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Immune Homeostasis: A Novel Example of Teamwork

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Immune Homeostasis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2782))

Abstract

All living organisms must maintain homeostasis to survive, reproduce, and pass their traits on to the next generation. If homeostasis is not maintained, it can result in various diseases and ultimately lead to death. Physiologists have coined the term “homeostasis” to describe this process. With the emergence of immunology as a separate branch of medicine, the concept of immune homeostasis has been introduced. Maintaining immune homeostasis is crucial to support overall homeostasis through different immunological and non-immunological routes. Any changes in the immune system can lead to chronic inflammatory or autoimmune diseases, immunodeficiency diseases, frequent infections, and cancers. Ongoing scientific advances are exploring new avenues in immunology and immune homeostasis maintenance. This chapter introduces the concept of immune homeostasis and its maintenance through different mechanisms.

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References

  1. Bernard C (1879) Leçons sur les phénomènes de la vie commune aux animaux et aux végétaux, vol 2. Baillière, Paris

    Book  Google Scholar 

  2. Damasio A, Damasio H (2016) Exploring the concept of homeostasis and considering its implications for economics. J Econ Behav Organ 126:125–129. https://doi.org/10.1016/j.jebo.2015.12.003

    Article  Google Scholar 

  3. Cannon WB (1929) Organization for physiological homeostasis. Physiol Rev 9(3):399–431. https://doi.org/10.1152/physrev.1929.9.3.399

    Article  Google Scholar 

  4. Nobs SP, Kopf M (2021) Tissue-resident macrophages: guardians of organ homeostasis. Trends Immunol 42(6):495–507. https://doi.org/10.1016/j.it.2021.04.007

    Article  CAS  PubMed  Google Scholar 

  5. Gray JI, Farber DL (2022) Tissue-resident immune cells in humans. Annu Rev Immunol 40:195–220. https://doi.org/10.1146/annurev-immunol-093019-112809

    Article  CAS  PubMed  Google Scholar 

  6. Gebhardt T, Palendira U, Tscharke DC, Bedoui S (2018) Tissue-resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance. Immunol Rev 283(1):54–76. https://doi.org/10.1111/imr.12650

    Article  CAS  PubMed  Google Scholar 

  7. Parijs LV, Abbas AK (1998) Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 280(5361):243–248. https://doi.org/10.1126/science.280.5361.243

    Article  PubMed  Google Scholar 

  8. Chatenoud L (2014) Teaching the immune system “self” respect and tolerance. Science 344(6190):1343–1344. https://doi.org/10.1126/science.1256864

    Article  CAS  PubMed  Google Scholar 

  9. Halper-Stromberg A, Jabri B (2022) Maladaptive consequences of inflammatory events shape individual immune identity. Nat Immunol 23(12):1675–1686. https://doi.org/10.1038/s41590-022-01342-8

    Article  CAS  PubMed  Google Scholar 

  10. Dessie ZG, Zewotir T (2021) Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis 21(1):855. https://doi.org/10.1186/s12879-021-06536-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Caramelo F, Ferreira N, Oliveiros B (2020) Estimation of risk factors for COVID-19 mortality – preliminary results. medRxiv, 2020.2002.2024.20027268. https://doi.org/10.1101/2020.02.24.20027268

  12. Booth A, Reed AB, Ponzo S, Yassaee A, Aral M, Plans D et al (2021) Population risk factors for severe disease and mortality in COVID-19: a global systematic review and meta-analysis. PLoS One 16(3):e0247461. https://doi.org/10.1371/journal.pone.0247461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wijeyesinghe S, Beura LK, Pierson MJ, Stolley JM, Adam OA, Ruscher R et al (2021) Expansible residence decentralizes immune homeostasis. Nature 592(7854):457–462. https://doi.org/10.1038/s41586-021-03351-3

    Article  CAS  PubMed  Google Scholar 

  14. Huan Y, Kong Q, Mou H, Yi H (2020) Antimicrobial peptides: classification, design, application and research progress in multiple fields [review]. Front Microbiol 11. https://doi.org/10.3389/fmicb.2020.582779

  15. Kościuczuk EM, Lisowski P, Jarczak J, Strzałkowska N, Jóźwik A, Horbańczuk J et al (2012) Cathelicidins: family of antimicrobial peptides. A review. Mol Biol Rep 39(12):10957–10970. https://doi.org/10.1007/s11033-012-1997-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kumar V (2019) Inflammation research sails through the sea of immunology to reach immunometabolism. Int Immunopharmacol 73:128–145. https://doi.org/10.1016/j.intimp.2019.05.002

    Article  CAS  PubMed  Google Scholar 

  17. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK (2002) Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16(2):219–230. https://doi.org/10.1016/s1074-7613(02)00274-1

    Article  CAS  PubMed  Google Scholar 

  18. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3(10):944–950. https://doi.org/10.1038/ni833

    Article  CAS  PubMed  Google Scholar 

  19. Mauri C, Gray D, Mushtaq N, Londei M (2003) Prevention of arthritis by interleukin 10-producing B cells. J Exp Med 197(4):489–501. https://doi.org/10.1084/jem.20021293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dikiy S, Rudensky AY (2023) Principles of regulatory T cell function. Immunity 56(2):240–255. https://doi.org/10.1016/j.immuni.2023.01.004

    Article  CAS  PubMed  Google Scholar 

  21. Headland SE, Norling LV (2015) The resolution of inflammation: principles and challenges. Semin Immunol 27(3):149–160. https://doi.org/10.1016/j.smim.2015.03.014

    Article  CAS  PubMed  Google Scholar 

  22. Watanabe S, Alexander M, Misharin AV, Budinger GRS (2019) The role of macrophages in the resolution of inflammation. J Clin Invest 129(7):2619–2628. https://doi.org/10.1172/JCI124615

    Article  PubMed  PubMed Central  Google Scholar 

  23. Caravaca AS, Gallina AL, Tarnawski L, Shavva VS, Colas RA, Dalli J et al (2022) Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit. Proc Natl Acad Sci 119(22):e2023285119. https://doi.org/10.1073/pnas.2023285119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Feehan KT, Gilroy DW (2019) Is resolution the end of inflammation? Trends Mol Med 25(3):198–214. https://doi.org/10.1016/j.molmed.2019.01.006

    Article  CAS  PubMed  Google Scholar 

  25. Fullerton JN, Gilroy DW (2016) Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discov 15(8):551–567. https://doi.org/10.1038/nrd.2016.39

    Article  CAS  PubMed  Google Scholar 

  26. Mills CD (2012) M1 and M2 macrophages: oracles of health and disease. Crit Rev Immunol 32(6):463–488. https://doi.org/10.1615/critrevimmunol.v32.i6.10

    Article  CAS  PubMed  Google Scholar 

  27. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L et al (2009) Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 16(3):183–194. https://doi.org/10.1016/j.ccr.2009.06.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nicolás-Ávila JÁ, Adrover JM, Hidalgo A (2017) Neutrophils in homeostasis, immunity, and cancer. Immunity 46(1):15–28. https://doi.org/10.1016/j.immuni.2016.12.012

    Article  CAS  PubMed  Google Scholar 

  29. Mauri C, Bosma A (2012) Immune regulatory function of B cells. Annu Rev Immunol 30(1):221–241. https://doi.org/10.1146/annurev-immunol-020711-074934

    Article  CAS  PubMed  Google Scholar 

  30. Rosser EC, Mauri C (2015) Regulatory B cells: origin, phenotype, and function. Immunity 42(4):607–612. https://doi.org/10.1016/j.immuni.2015.04.005

    Article  CAS  PubMed  Google Scholar 

  31. Vignali DA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8(7):523–532. https://doi.org/10.1038/nri2343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Beissert S, Schwarz A, Schwarz T (2006) Regulatory T cells. J Investig Dermatol 126(1):15–24. https://doi.org/10.1038/sj.jid.5700004

    Article  CAS  PubMed  Google Scholar 

  33. Dominguez-Villar M, Hafler DA (2018) Regulatory T cells in autoimmune disease. Nat Immunol 19(7):665–673. https://doi.org/10.1038/s41590-018-0120-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174. https://doi.org/10.1038/nri2506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Veglia F, Sanseviero E, Gabrilovich DI (2021) Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol 21(8):485–498. https://doi.org/10.1038/s41577-020-00490-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454(7203):428–435. https://doi.org/10.1038/nature07201

    Article  CAS  PubMed  Google Scholar 

  37. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140(6):883–899. https://doi.org/10.1016/j.cell.2010.01.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C et al (2019) Chronic inflammation in the etiology of disease across the life span. Nat Med 25(12):1822–1832. https://doi.org/10.1038/s41591-019-0675-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Thieblemont N, Wright HL, Edwards SW, Witko-Sarsat V (2016) Human neutrophils in auto-immunity. Semin Immunol 28(2):159–173. https://doi.org/10.1016/j.smim.2016.03.004

    Article  CAS  PubMed  Google Scholar 

  40. Kumar V, Stewart JH (2023) Immunometabolic reprogramming, another cancer hallmark [review]. Front Immunol 14. https://doi.org/10.3389/fimmu.2023.1125874

  41. Moses K, Brandau S (2016) Human neutrophils: their role in cancer and relation to myeloid-derived suppressor cells. Semin Immunol 28(2):187–196. https://doi.org/10.1016/j.smim.2016.03.018

    Article  CAS  PubMed  Google Scholar 

  42. Plitas G, Rudensky AY (2020) Regulatory T cells in cancer. Ann Rev Cancer Biol 4(1):459–477. https://doi.org/10.1146/annurev-cancerbio-030419-033428

    Article  Google Scholar 

  43. Togashi Y, Shitara K, Nishikawa H (2019) Regulatory T cells in cancer immunosuppression – implications for anticancer therapy. Nat Rev Clin Oncol 16(6):356–371. https://doi.org/10.1038/s41571-019-0175-7

    Article  CAS  PubMed  Google Scholar 

  44. Balkwill F, Montfort A, Capasso M (2013) B regulatory cells in cancer. Trends Immunol 34(4):169–173. https://doi.org/10.1016/j.it.2012.10.007

    Article  CAS  PubMed  Google Scholar 

  45. Sarvaria A, Madrigal JA, Saudemont A (2017) B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol 14(8):662–674. https://doi.org/10.1038/cmi.2017.35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Barry ST, Gabrilovich DI, Sansom OJ, Campbell AD, Morton JP (2023) Therapeutic targeting of tumour myeloid cells. Nat Rev Cancer 23:216. https://doi.org/10.1038/s41568-022-00546-2

    Article  CAS  PubMed  Google Scholar 

  47. Groth C, Hu X, Weber R, Fleming V, Altevogt P, Utikal J et al (2019) Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer 120(1):16–25. https://doi.org/10.1038/s41416-018-0333-1

    Article  CAS  PubMed  Google Scholar 

  48. Rehwinkel J, Gack MU (2020) RIG-I-like receptors: their regulation and roles in RNA sensing. Nat Rev Immunol 20(9):537–551. https://doi.org/10.1038/s41577-020-0288-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Geijtenbeek TBH, Gringhuis SI (2009) Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9(7):465–479. https://doi.org/10.1038/nri2569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yamada T, Takaoka A (2023) Innate immune recognition against SARS-CoV-2. Inflamm Regen 43(1):7. https://doi.org/10.1186/s41232-023-00259-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Brown GD, Willment JA, Whitehead L (2018) C-type lectins in immunity and homeostasis. Nat Rev Immunol 18(6):374–389. https://doi.org/10.1038/s41577-018-0004-8

    Article  CAS  PubMed  Google Scholar 

  52. Li D, Wu M (2021) Pattern recognition receptors in health and diseases. Signal Transduct Target Ther 6(1):291. https://doi.org/10.1038/s41392-021-00687-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kumar V (2019) The complement system, toll-like receptors and inflammasomes in host defense: three musketeers’ one target. Int Rev Immunol 38(4):131–156. https://doi.org/10.1080/08830185.2019.1609962

    Article  CAS  PubMed  Google Scholar 

  54. Kumar V (2018) Toll-like receptors in immunity and inflammatory diseases: past, present, and future. Int Immunopharmacol 59:391–412. https://doi.org/10.1016/j.intimp.2018.03.002

    Article  CAS  Google Scholar 

  55. Kumar V (2020) The trinity of cGAS, TLR9, and ALRs guardians of the cellular galaxy against host-derived self-DNA. Front Immunol 11:624597. https://doi.org/10.3389/fimmu.2020.624597

    Article  CAS  PubMed  Google Scholar 

  56. Murugaiah V, Varghese PM, Beirag N, De Cordova S, Sim RB, Kishore U (2021) Complement proteins as soluble pattern recognition receptors for pathogenic viruses. Viruses 13(5). https://doi.org/10.3390/v13050824

  57. Gradzka-Boberda S, Gentle Ian E, Häcker G (2022) Pattern recognition receptors of nucleic acids can cause sublethal activation of the mitochondrial apoptosis pathway during viral infection. J Virol 96(18):e01212–e01222. https://doi.org/10.1128/jvi.01212-22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zevini A, Olagnier D, Hiscott J (2017) Crosstalk between cytoplasmic RIG-I and STING sensing pathways. Trends Immunol 38(3):194–205. https://doi.org/10.1016/j.it.2016.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kumar V (2022) Toll-like receptors in adaptive immunity. Handb Exp Pharmacol 276:95–131. https://doi.org/10.1007/164_2021_543

    Article  CAS  PubMed  Google Scholar 

  60. Jiang Y, Zhang H, Wang J, Chen J, Guo Z, Liu Y et al (2023) Exploiting RIG-I-like receptor pathway for cancer immunotherapy. J Hematol Oncol 16(1):8. https://doi.org/10.1186/s13045-023-01405-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kumar V (2021) Going, toll-like receptors in skin inflammation and inflammatory diseases. EXCLI J 20:52–79. https://doi.org/10.17179/excli2020-3114

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kumar V, Barrett JE (2022) Toll-like receptors (TLRs) in health and disease: an overview. Handb Exp Pharmacol 276:1–21. https://doi.org/10.1007/164_2021_568

    Article  CAS  PubMed  Google Scholar 

  63. Kumar V (2019) A STING to inflammation and autoimmunity. J Leukoc Biol 106(1):171–185. https://doi.org/10.1002/jlb.4mir1018-397rr

    Article  CAS  PubMed  Google Scholar 

  64. Kumar V (2019) Toll-like receptors in the pathogenesis of neuroinflammation. J Neuroimmunol 332:16–30. https://doi.org/10.1016/j.jneuroim.2019.03.012

    Article  CAS  PubMed  Google Scholar 

  65. Kigerl KA, de Rivero Vaccari JP, Dietrich WD, Popovich PG, Keane RW (2014) Pattern recognition receptors and central nervous system repair. Exp Neurol 258:5–16. https://doi.org/10.1016/j.expneurol.2014.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Li L, Acioglu C, Heary RF, Elkabes S (2021) Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases. Brain Behav Immun 91:740–755. https://doi.org/10.1016/j.bbi.2020.10.007

    Article  CAS  PubMed  Google Scholar 

  67. Rumpret M, von Richthofen HJ, Peperzak V, Meyaard L (2021) Inhibitory pattern recognition receptors. J Exp Med 219(1):e20211463. https://doi.org/10.1084/jem.20211463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cario E, Brown D, McKee M, Lynch-Devaney K, Gerken G, Podolsky DK (2002) Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium. Am J Pathol 160(1):165–173. https://doi.org/10.1016/s0002-9440(10)64360-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tukaj S, Kaminski M (2019) Heat shock proteins in the therapy of autoimmune diseases: too simple to be true? Cell Stress Chaperones 24(3):475–479. https://doi.org/10.1007/s12192-019-01000-3

    Article  PubMed  PubMed Central  Google Scholar 

  70. Broere F, van der Zee R, van Eden W (2011) Heat shock proteins are no DAMPs, rather ‘DAMPERs’. Nat Rev Immunol 11(8):565–565. https://doi.org/10.1038/nri2873-c1

    Article  CAS  PubMed  Google Scholar 

  71. Nozaki K, Li L, Miao EA (2022) Innate sensors trigger regulated cell death to combat intracellular infection. Annu Rev Immunol 40(1):469–498. https://doi.org/10.1146/annurev-immunol-101320-011235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13(10):722–737. https://doi.org/10.1038/nri3532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Brubaker SW, Bonham KS, Zanoni I, Kagan JC (2015) Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol 33(1):257–290. https://doi.org/10.1146/annurev-immunol-032414-112240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Vollmer J (2009) Autophagy links pattern recognition receptors to tumor cell apoptosis. Mol Ther 17(11):1839–1841. https://doi.org/10.1038/mt.2009.241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Shekarian T, Valsesia-Wittmann S, Brody J, Michallet MC, Depil S, Caux C et al (2017) Pattern recognition receptors: immune targets to enhance cancer immunotherapy. Ann Oncol 28(8):1756–1766. https://doi.org/10.1093/annonc/mdx179

    Article  CAS  PubMed  Google Scholar 

  76. Zhu G, Xu Y, Cen X, Nandakumar KS, Liu S, Cheng K (2018) Targeting pattern-recognition receptors to discover new small molecule immune modulators. Eur J Med Chem 144:82–92. https://doi.org/10.1016/j.ejmech.2017.12.026

    Article  CAS  PubMed  Google Scholar 

  77. Yuki K, Koutsogiannaki S (2021) Pattern recognition receptors as therapeutic targets for bacterial, viral and fungal sepsis. Int Immunopharmacol 98:107909. https://doi.org/10.1016/j.intimp.2021.107909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. McKernan DP (2020) Chapter three. Pattern recognition receptors as potential drug targets in inflammatory disorders. In: Donev R (ed) Advances in protein chemistry and structural biology, vol 119. Academic Press, pp 65–109

    Google Scholar 

  79. Deans C, Maggert KA (2015) What do you mean, “epigenetic”? Genetics 199(4):887–896. https://doi.org/10.1534/genetics.114.173492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Liotti A, Ferrara AL, Loffredo S, Galdiero MR, Varricchi G, Di Rella F et al (2022) Epigenetics: an opportunity to shape innate and adaptive immune responses. Immunology 167(4):451–470. https://doi.org/10.1111/imm.13571

    Article  CAS  PubMed  Google Scholar 

  81. Prokopuk L, Western PS, Stringer JM (2015) Transgenerational epigenetic inheritance: adaptation through the germline epigenome? Epigenomics 7(5):829–846. https://doi.org/10.2217/epi.15.36

    Article  CAS  PubMed  Google Scholar 

  82. Chen MA, LeRoy AS, Majd M, Chen JY, Brown RL, Christian LM et al (2021) Immune and epigenetic pathways linking childhood adversity and health across the lifespan. Front Psychol 12:788351. https://doi.org/10.3389/fpsyg.2021.788351

    Article  PubMed  PubMed Central  Google Scholar 

  83. Fagundes CP, Glaser R, Kiecolt-Glaser JK (2013) Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav Immun 27(1):8–12. https://doi.org/10.1016/j.bbi.2012.06.014

    Article  CAS  PubMed  Google Scholar 

  84. Reemst K, Kracht L, Kotah JM, Rahimian R, van Irsen AAS, Congrains Sotomayor G et al (2022) Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions. Transl Psychiatry 12(1):507. https://doi.org/10.1038/s41398-022-02265-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Slopen N, Loucks EB, Appleton AA, Kawachi I, Kubzansky LD, Non AL et al (2015) Early origins of inflammation: an examination of prenatal and childhood social adversity in a prospective cohort study. Psychoneuroendocrinology 51:403–413. https://doi.org/10.1016/j.psyneuen.2014.10.016

    Article  CAS  PubMed  Google Scholar 

  86. Wimmers F, Donato M, Kuo A, Ashuach T, Gupta S, Li C et al (2021) The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination. Cell 184(15):3915–3935.e3921. https://doi.org/10.1016/j.cell.2021.05.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Xiao C, Rajewsky K (2009) MicroRNA control in the immune system: basic principles. Cell 136(1):26–36. https://doi.org/10.1016/j.cell.2008.12.027

    Article  CAS  PubMed  Google Scholar 

  88. Lindsay MA (2008) microRNAs and the immune response. Trends Immunol 29(7):343–351. https://doi.org/10.1016/j.it.2008.04.004

    Article  CAS  PubMed  Google Scholar 

  89. Mehta A, Baltimore D (2016) MicroRNAs as regulatory elements in immune system logic. Nat Rev Immunol 16(5):279–294. https://doi.org/10.1038/nri.2016.40

    Article  CAS  PubMed  Google Scholar 

  90. Zhang Q, Cao X (2019) Epigenetic regulation of the innate immune response to infection. Nat Rev Immunol 19(7):417–432. https://doi.org/10.1038/s41577-019-0151-6

    Article  CAS  PubMed  Google Scholar 

  91. Busslinger M, Tarakhovsky A (2014) Epigenetic control of immunity. Cold Spring Harb Perspect Biol 6(6). https://doi.org/10.1101/cshperspect.a019307

  92. Placek K, Schultze JL, Aschenbrenner AC (2019) Epigenetic reprogramming of immune cells in injury, repair, and resolution. J Clin Invest 129(8):2994–3005. https://doi.org/10.1172/JCI124619

    Article  PubMed  PubMed Central  Google Scholar 

  93. Chen S, Yang J, Wei Y, Wei X (2020) Epigenetic regulation of macrophages: from homeostasis maintenance to host defense. Cell Mol Immunol 17(1):36–49. https://doi.org/10.1038/s41423-019-0315-0

    Article  CAS  PubMed  Google Scholar 

  94. Perkins DJ, Patel MC, Blanco JC, Vogel SN (2016) Epigenetic mechanisms governing innate inflammatory responses. J Interf Cytokine Res 36(7):454–461. https://doi.org/10.1089/jir.2016.0003

    Article  CAS  Google Scholar 

  95. Feerick C, McKernan DP (2017) Epigenetic modifications influence NOD-like receptor expression and associated pro-inflammatory activity. FASEB J 31(S1):1060.1062-1060.1062. https://doi.org/10.1096/fasebj.31.1_supplement.1060.2

    Article  Google Scholar 

  96. Morandini AC, Santos CF, Yilmaz Ö (2016) Role of epigenetics in modulation of immune response at the junction of host-pathogen interaction and danger molecule signaling. Pathog Dis 74(7):ftw082. https://doi.org/10.1093/femspd/ftw082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Mehta S, Jeffrey KL (2016) Chapter 12. Immune system disorders and epigenetics. In: Tollefsbol TO (ed) Medical epigenetics. Academic Press, Boston, pp 199–219

    Chapter  Google Scholar 

  98. Campos-Sanchez E, Martínez-Cano J, del Pino Molina L, López-Granados E, Cobaleda C (2019) Epigenetic deregulation in human primary immunodeficiencies. Trends Immunol 40(1):49–65. https://doi.org/10.1016/j.it.2018.11.005

    Article  CAS  PubMed  Google Scholar 

  99. Rae W (2017) Indications to epigenetic dysfunction in the pathogenesis of common variable immunodeficiency. Arch Immunol Ther Exp 65(2):101–110. https://doi.org/10.1007/s00005-016-0414-x

    Article  CAS  Google Scholar 

  100. Martínez-Cano J, Campos-Sánchez E, Cobaleda C (2019) Epigenetic priming in immunodeficiencies. Front Cell Dev Biol 7:125. https://doi.org/10.3389/fcell.2019.00125

    Article  PubMed  PubMed Central  Google Scholar 

  101. Campos-Sanchez E, Martínez-Cano J, Del Pino Molina L, López-Granados E, Cobaleda C (2019) Epigenetic deregulation in human primary immunodeficiencies. Trends Immunol 40(1):49–65. https://doi.org/10.1016/j.it.2018.11.005

    Article  CAS  PubMed  Google Scholar 

  102. Rodríguez-Ubreva J, Arutyunyan A, Bonder MJ, Del Pino-Molina L, Clark SJ, de la Calle-Fabregat C et al (2022) Single-cell atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses. Nat Commun 13(1):1779. https://doi.org/10.1038/s41467-022-29450-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Scharer CD, Blalock EL, Mi T, Barwick BG, Jenks SA, Deguchi T et al (2019) Epigenetic programming underpins B cell dysfunction in human SLE. Nat Immunol 20(8):1071–1082. https://doi.org/10.1038/s41590-019-0419-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Moroney JB, Vasudev A, Pertsemlidis A, Zan H, Casali P (2020) Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells. Nat Commun 11(1):5435. https://doi.org/10.1038/s41467-020-19242-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Xiao F, Rui K, Shi X, Wu H, Cai X, Lui KO et al (2022) Epigenetic regulation of B cells and its role in autoimmune pathogenesis. Cell Mol Immunol 19(11):1215–1234. https://doi.org/10.1038/s41423-022-00933-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Godoy-Tena G, Barmada A, Morante-Palacios O, de la Calle-Fabregat C, Martins-Ferreira R, Ferreté-Bonastre AG et al (2022) Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines. Genome Med 14(1):134. https://doi.org/10.1186/s13073-022-01137-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Wu D, Shi Y, Zhang H, Miao C (2023) Epigenetic mechanisms of immune remodeling in sepsis: targeting histone modification. Cell Death Dis 14(2):112. https://doi.org/10.1038/s41419-023-05656-9

    Article  PubMed  PubMed Central  Google Scholar 

  108. Belk JA, Daniel B, Satpathy AT (2022) Epigenetic regulation of T cell exhaustion. Nat Immunol 23(6):848–860. https://doi.org/10.1038/s41590-022-01224-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Tien F-M, Lu H-H, Lin S-Y, Tsai H-C (2023) Epigenetic remodeling of the immune landscape in cancer: therapeutic hurdles and opportunities. J Biomed Sci 30(1):3. https://doi.org/10.1186/s12929-022-00893-0

    Article  PubMed  PubMed Central  Google Scholar 

  110. Palma-Gudiel H, Prather AA, Lin J, Oxendine JD, Guintivano J, Xia K et al (2021) HPA axis regulation and epigenetic programming of immune-related genes in chronically stressed and non-stressed mid-life women. Brain Behav Immun 92:49–56. https://doi.org/10.1016/j.bbi.2020.11.027

    Article  CAS  PubMed  Google Scholar 

  111. Chatzittofis A, Boström ADE, Ciuculete DM, Öberg KG, Arver S, Schiöth HB et al (2021) HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes. Sci Rep 11(1):20134. https://doi.org/10.1038/s41598-021-99714-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B et al (2011) Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet 156b(6):700–708. https://doi.org/10.1002/ajmg.b.31212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Uddin M, Aiello AE, Wildman DE, Koenen KC, Pawelec G, de los Santos R et al (2010) Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proc Natl Acad Sci U S A 107(20):9470–9475. https://doi.org/10.1073/pnas.0910794107

    Article  PubMed  PubMed Central  Google Scholar 

  114. Scheiermann C, Kunisaki Y, Frenette PS (2013) Circadian control of the immune system. Nat Rev Immunol 13(3):190–198. https://doi.org/10.1038/nri3386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Scheiermann C, Gibbs J, Ince L, Loudon A (2018) Clocking in to immunity. Nat Rev Immunol 18(7):423–437. https://doi.org/10.1038/s41577-018-0008-4

    Article  CAS  PubMed  Google Scholar 

  116. Pearson JA, Wong FS, Wen L (2020) Crosstalk between circadian rhythms and the microbiota. Immunology 161(4):278–290. https://doi.org/10.1111/imm.13278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Taylor L, Von Lendenfeld F, Ashton A, Sanghani H, Di Pretoro S, Usselmann L et al (2023) Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection. iScience 26(2):105877. https://doi.org/10.1016/j.isci.2022.105877

    Article  PubMed  Google Scholar 

  118. Crislip GR, Johnston JG, Douma LG, Costello HM, Juffre A, Boyd K et al (2021) Circadian rhythm effects on the molecular regulation of physiological systems. Compr Physiol 12(1):2769–2798. https://doi.org/10.1002/cphy.c210011

    Article  PubMed  Google Scholar 

  119. Kiess W, Belohradsky BH (1986) Endocrine regulation of the immune system. Klin Wochenschr 64(1):1–7. https://doi.org/10.1007/bf01721574

    Article  CAS  PubMed  Google Scholar 

  120. Webster JI, Tonelli L, Sternberg EM (2002) Neuroendocrine regulation of immunity. Annu Rev Immunol 20(1):125–163. https://doi.org/10.1146/annurev.immunol.20.082401.104914

    Article  CAS  PubMed  Google Scholar 

  121. Arrieta M-C, Finlay B (2012) The commensal microbiota drives immune homeostasis [mini review]. Front Immunol 3. https://doi.org/10.3389/fimmu.2012.00033

  122. Honda K, Littman DR (2016) The microbiota in adaptive immune homeostasis and disease. Nature 535(7610):75–84. https://doi.org/10.1038/nature18848

    Article  CAS  PubMed  Google Scholar 

  123. Bishehsari F, Voigt RM, Keshavarzian A (2020) Circadian rhythms and the gut microbiota: from the metabolic syndrome to cancer. Nat Rev Endocrinol 16(12):731–739. https://doi.org/10.1038/s41574-020-00427-4

    Article  PubMed  PubMed Central  Google Scholar 

  124. Sato T, Sassone-Corsi P (2022) Nutrition, metabolism, and epigenetics: pathways of circadian reprogramming. EMBO Rep 23(5):e52412. https://doi.org/10.15252/embr.202152412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Coulson RL, LaSalle JM (2018) Epigenetics of circadian rhythms in imprinted neurodevelopmental disorders. In: Grayson DR (ed) Progress in molecular biology and translational science, vol 157. Academic Press, pp 67–92

    Google Scholar 

  126. Masri S, Kinouchi K, Sassone-Corsi P (2015) Circadian clocks, epigenetics, and cancer. Curr Opin Oncol 27(1):50–56. https://doi.org/10.1097/cco.0000000000000153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Aguilera M, Gálvez-Ontiveros Y, Rivas A (2020) Endobolome, a new concept for determining the influence of microbiota disrupting chemicals (MDC) in relation to specific endocrine pathogenesis [review]. Front Microbiol 11. https://doi.org/10.3389/fmicb.2020.578007

  128. Williams CL, Garcia-Reyero N, Martyniuk CJ, Tubbs CW, Bisesi JH (2020) Regulation of endocrine systems by the microbiome: perspectives from comparative animal models. Gen Comp Endocrinol 292:113437. https://doi.org/10.1016/j.ygcen.2020.113437

    Article  CAS  PubMed  Google Scholar 

  129. Morris DJ, Ridlon JM (2017) Glucocorticoids and gut bacteria: “The GALF Hypothesis” in the metagenomic era. Steroids 125:1–13. https://doi.org/10.1016/j.steroids.2017.06.002

    Article  CAS  PubMed  Google Scholar 

  130. Cussotto S, Sandhu KV, Dinan TG, Cryan JF (2018) The neuroendocrinology of the microbiota-gut-brain axis: a behavioural perspective. Front Neuroendocrinol 51:80–101. https://doi.org/10.1016/j.yfrne.2018.04.002

    Article  CAS  PubMed  Google Scholar 

  131. Jaggar M, Rea K, Spichak S, Dinan TG, Cryan JF (2020) You’ve got male: sex and the microbiota-gut-brain axis across the lifespan. Front Neuroendocrinol 56:100815. https://doi.org/10.1016/j.yfrne.2019.100815

    Article  PubMed  Google Scholar 

  132. Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P, Becker L et al (2013) Gender bias in autoimmunity is influenced by microbiota. Immunity 39(2):400–412. https://doi.org/10.1016/j.immuni.2013.08.013

    Article  CAS  PubMed  Google Scholar 

  133. Chen KL, Madak-Erdogan Z (2016) Estrogen and microbiota crosstalk: should we pay attention? Trends Endocrinol Metab 27(11):752–755. https://doi.org/10.1016/j.tem.2016.08.001

    Article  CAS  PubMed  Google Scholar 

  134. Bistoletti M, Bosi A, Banfi D, Giaroni C, Baj A (2020) Chapter two. The microbiota-gut-brain axis: focus on the fundamental communication pathways. In: Kasselman LJ (ed) Progress in molecular biology and translational science, vol 176. Academic Press, pp 43–110

    Google Scholar 

  135. El Aidy S, Dinan TG, Cryan JF (2015) Gut microbiota: the conductor in the orchestra of immune–neuroendocrine communication. Clin Ther 37(5):954–967. https://doi.org/10.1016/j.clinthera.2015.03.002

    Article  CAS  PubMed  Google Scholar 

  136. Wensveen FM, Šestan M, Turk Wensveen T, Polić B (2019) ‘Beauty and the beast’ in infection: how immune–endocrine interactions regulate systemic metabolism in the context of infection. Eur J Immunol 49(7):982–995. https://doi.org/10.1002/eji.201847895

    Article  CAS  PubMed  Google Scholar 

  137. Anderson AC, Acharya N (2022) Steroid hormone regulation of immune responses in cancer. Immunometabolism 4(4):e00012

    Article  PubMed  Google Scholar 

  138. Paavonen T (1994) Hormonal regulation of immune responses. Ann Med 26(4):255–258. https://doi.org/10.3109/07853899409147900

    Article  CAS  PubMed  Google Scholar 

  139. Klein Wolterink RGJ, Wu GS, Chiu IM, Veiga-Fernandes H (2022) Neuroimmune interactions in peripheral organs. Annu Rev Neurosci 45:339–360. https://doi.org/10.1146/annurev-neuro-111020-105359

    Article  CAS  PubMed  Google Scholar 

  140. Godinho-Silva C, Cardoso F, Veiga-Fernandes H (2019) Neuro-immune cell units: a new paradigm in physiology. Annu Rev Immunol 37:19–46. https://doi.org/10.1146/annurev-immunol-042718-041812

    Article  CAS  PubMed  Google Scholar 

  141. Chesné J, Cardoso V, Veiga-Fernandes H (2019) Neuro-immune regulation of mucosal physiology. Mucosal Immunol 12(1):10–20. https://doi.org/10.1038/s41385-018-0063-y

    Article  CAS  PubMed  Google Scholar 

  142. Chu C, Artis D, Chiu IM (2020) Neuro-immune interactions in the tissues. Immunity 52(3):464–474. https://doi.org/10.1016/j.immuni.2020.02.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Meixiong J, Basso L, Dong X, Gaudenzio N (2020) Nociceptor–mast cell sensory clusters as regulators of skin homeostasis. Trends Neurosci 43(3):130–132. https://doi.org/10.1016/j.tins.2020.01.001

    Article  CAS  PubMed  Google Scholar 

  144. Veiga-Fernandes H, Artis D (2018) Neuronal–immune system cross-talk in homeostasis. Science 359(6383):1465–1466. https://doi.org/10.1126/science.aap9598

    Article  PubMed  Google Scholar 

  145. Yu LW, Agirman G, Hsiao EY (2022) The gut microbiome as a regulator of the neuroimmune landscape. Annu Rev Immunol 40:143–167. https://doi.org/10.1146/annurev-immunol-101320-014237

    Article  CAS  PubMed  Google Scholar 

  146. Jacobson A, Yang D, Vella M, Chiu IM (2021) The intestinal neuro-immune axis: crosstalk between neurons, immune cells, and microbes. Mucosal Immunol 14(3):555–565. https://doi.org/10.1038/s41385-020-00368-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Domingues RG, Hepworth MR (2020) Immunoregulatory sensory circuits in Group 3 innate lymphoid cell (ILC3) function and tissue homeostasis. Front Immunol 11:116. https://doi.org/10.3389/fimmu.2020.00116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Konsman JP, Parnet P, Dantzer R (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25(3):154–159. https://doi.org/10.1016/s0166-2236(00)02088-9

    Article  CAS  PubMed  Google Scholar 

  149. McCusker RH, Kelley KW (2013) Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol 216(Pt 1):84–98. https://doi.org/10.1242/jeb.073411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56. https://doi.org/10.1038/nrn2297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Dantzer R (2006) Cytokine, sickness behavior, and depression. Neurol Clin 24(3):441–460. https://doi.org/10.1016/j.ncl.2006.03.003

    Article  PubMed  PubMed Central  Google Scholar 

  152. Leon LR (2002) Invited review: cytokine regulation of fever: studies using gene knockout mice. J Appl Physiol 92(6):2648–2655. https://doi.org/10.1152/japplphysiol.01005.2001

    Article  CAS  PubMed  Google Scholar 

  153. Blomqvist A, Engblom D (2018) Neural mechanisms of inflammation-induced fever. Neuroscientist 24(4):381–399. https://doi.org/10.1177/1073858418760481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Shao L, Pang N, Yan P, Jia F, Sun Q, Ma W et al (2018) Control of body temperature and immune function in patients undergoing open surgery for gastric cancer. Bosn J Basic Med Sci 18(3):289–296. https://doi.org/10.17305/bjbms.2018.2552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Evans SS, Repasky EA, Fisher DT (2015) Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol 15(6):335–349. https://doi.org/10.1038/nri3843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Wang F, Kim BS (2020) Itch: a paradigm of neuroimmune crosstalk. Immunity 52(5):753–766. https://doi.org/10.1016/j.immuni.2020.04.008

    Article  CAS  PubMed  Google Scholar 

  157. Mack MR, Kim BS (2018) The itch–scratch cycle: a neuroimmune perspective. Trends Immunol 39(12):980–991. https://doi.org/10.1016/j.it.2018.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Trier AM, Kim BS (2018) Cytokine modulation of atopic itch. Curr Opin Immunol 54:7–12. https://doi.org/10.1016/j.coi.2018.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Solinski HJ, Kriegbaum MC, Tseng P-Y, Earnest TW, Gu X, Barik A et al (2019) Nppb neurons are sensors of mast cell-induced itch. Cell Rep 26(13):3561–3573.e3564. https://doi.org/10.1016/j.celrep.2019.02.089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ et al (2017) Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell 171(1):217–228.e213. https://doi.org/10.1016/j.cell.2017.08.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Hashimoto T, Yosipovitch G (2019) Itching as a systemic disease. J Allergy Clin Immunol 144(2):375–380. https://doi.org/10.1016/j.jaci.2019.04.005

    Article  PubMed  Google Scholar 

  162. Pinho-Ribeiro FA, Verri WA Jr, Chiu IM (2017) Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol 38(1):5–19. https://doi.org/10.1016/j.it.2016.10.001

    Article  CAS  PubMed  Google Scholar 

  163. Baral P, Udit S, Chiu IM (2019) Pain and immunity: implications for host defence. Nat Rev Immunol 19(7):433–447. https://doi.org/10.1038/s41577-019-0147-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Cook AD, Christensen AD, Tewari D, McMahon SB, Hamilton JA (2018) Immune cytokines and their receptors in inflammatory pain. Trends Immunol 39(3):240–255. https://doi.org/10.1016/j.it.2017.12.003

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Surgery, Laboratory of Tumor Immunology and Immunotherapy, Medical Education Building-C, Morehouse School of Medicine, Atlanta, GA, USA

    Vijay Kumar & John H. Stewart IV

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Kumar, V., Stewart, J.H. (2024). Immune Homeostasis: A Novel Example of Teamwork. In: Kumar, V. (eds) Immune Homeostasis. Methods in Molecular Biology, vol 2782. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3754-8_1

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