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Innate lymphoid cells—key immune integrators of overall body homeostasis

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Abstract

The maintenance of the tissue barrier is essential to protect the host from external pathogens, thus ensuring the survival of the organism. This process requires the integration of various physiological signals originating from the digestive, immune, endocrine, and the nervous system as indicators of overall body fitness. Innate lymphoid cells (ILC) are a group of immune cells equipped for the guarding and maintenance of the tissue barrier against invading pathogens. Extensive research has focused on the regulation of ILC by cytokines derived from immune or non-immune cells, such as the epithelium. However, recent findings suggest that ILC may play an additional role in the monitoring of the overall health status of the host. This requires the combined sensing of cytokines, metabolites, hormones, and neuropeptides. ILC appear to be essential in this process functioning as hubs for the integration of different physiological signals to facilitate barrier immunity. Here, we discuss the emerging literature revealing dietary, metabolic, hormonal, and neuronal signals as important controllers and modulators of ILC function in health and disease.

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References

  1. Sonnenberg GF, Artis D (2015) Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med 21:698–708. https://doi.org/10.1038/nm.3892

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Eberl G, Colonna M, Di Santo JP, McKenzie ANJ (2015) Innate lymphoid cells: a new paradigm in immunology. Science (80-) 348:aaa6566. https://doi.org/10.1126/science.aaa6566

    Article  CAS  Google Scholar 

  3. Liu M, Zhang C (2017) The role of innate lymphoid cells in immune-mediated liver diseases. Front Immunol 8:695. https://doi.org/10.3389/fimmu.2017.00695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Xiong T, Turner J (2018) Innate lymphoid cells in autoimmunity and chronic inflammatory diseases. Semin Immunopathol. https://doi.org/10.1007/s00281-018-0670-4

  5. Spits H, Artis D, Colonna M, Diefenbach A, di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE, Powrie F, Vivier E (2013) Innate lymphoid cells-a proposal for uniform nomenclature. Nat Rev Immunol 13:145–149. https://doi.org/10.1038/nri3365

    Article  PubMed  CAS  Google Scholar 

  6. Constantinides MG, McDonald BD, Verhoef PA, Bendelac A (2014) A committed precursor to innate lymphoid cells. Nature 508:397–401. https://doi.org/10.1038/nature13047

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Klose CSN, Flach M, Möhle L, Rogell L, Hoyler T, Ebert K, Fabiunke C, Pfeifer D, Sexl V, Fonseca-Pereira D, Domingues RG, Veiga-Fernandes H, Arnold SJ, Busslinger M, Dunay IR, Tanriver Y, Diefenbach A (2014) Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157:340–356. https://doi.org/10.1016/j.cell.2014.03.030

    Article  PubMed  CAS  Google Scholar 

  8. Serafini N, Vosshenrich CAJ, Di Santo JP (2015) Transcriptional regulation of innate lymphoid cell fate. Nat Rev Immunol 15:415–428. https://doi.org/10.1038/nri3855

    Article  PubMed  CAS  Google Scholar 

  9. Fuchs A, Vermi W, Lee JS, Lonardi S, Gilfillan S, Newberry RD, Cella M, Colonna M (2013) Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-gamma-producing cells. Immunity 38(4):769–781. https://doi.org/10.1016/j.immuni.2013.02.010

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Bernink JH, Peters CP, Munneke M, te Velde AA, Meijer SL, Weijer K, Hreggvidsdottir HS, Heinsbroek SE, Legrand N, Buskens CJ, Bemelman WA, Mjösberg JM, Spits H (2013) Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol 14:221–229. https://doi.org/10.1038/ni2534

    Article  PubMed  CAS  Google Scholar 

  11. Zook EC, Kee BL (2016) Development of innate lymphoid cells. Nat Immunol 17:775–782. https://doi.org/10.1038/ni.3481

    Article  PubMed  CAS  Google Scholar 

  12. Artis D, Spits H (2015) The biology of innate lymphoid cells. Nature 517:293–301

    Article  PubMed  CAS  Google Scholar 

  13. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa JI, Ohtani M, Fujii H, Koyasu S (2010) Innate production of TH2 cytokines by adipose tissue-associated c-kit+Sca-1+ lymphoid cells. Nature 463:540–544. https://doi.org/10.1038/nature08636

    Article  PubMed  CAS  Google Scholar 

  14. Price AE, Liang H-E, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, Locksley RM (2010) Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci 107:11489–11494. https://doi.org/10.1073/pnas.1003988107

    Article  PubMed  Google Scholar 

  15. Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T, Spits H (2011) Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol 12:1055–1062. https://doi.org/10.1038/ni.2104

    Article  PubMed  CAS  Google Scholar 

  16. Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CGK, Doering TA, Angelosanto JM, Laidlaw BJ, Yang CY, Sathaliyawala T, Kubota M, Turner D, Diamond JM, Goldrath AW, Farber DL, Collman RG, Wherry EJ, Artis D (2011) Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol 12:1045–1054. https://doi.org/10.1038/ni.2131

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JKM, Doherty JM, Mills JC, Colonna M (2009) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457:722–725. https://doi.org/10.1038/nature07537

    Article  PubMed  CAS  Google Scholar 

  18. Buonocore S, Ahern PP, Uhlig HH, Ivanov II, Littman DR, Maloy KJ, Powrie F (2010) Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464:1371–1375. https://doi.org/10.1038/nature08949

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Eder W, Ege MJ, von Mutius E (2006) The asthma epidemic. N Engl J Med 355:2226–2235. https://doi.org/10.1056/NEJMra054308

    Article  PubMed  CAS  Google Scholar 

  20. Maslowski KM, MacKay CR (2011) Diet, gut microbiota and immune responses. Nat Immunol 12:5–9

    Article  PubMed  CAS  Google Scholar 

  21. Strachan DP (1989) Hay fever, hygiene, and household size. BMJ 299:1259–1260. https://doi.org/10.1136/bmj.299.6710.1259

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Strachan DP (2000) Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 55(Suppl 1):S2–S10. https://doi.org/10.1136/thorax.55.suppl_1.S2

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wills-Karp M, Santeliz J, Karp CL (2001) The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 1:69–75. https://doi.org/10.1038/35095579

    Article  PubMed  CAS  Google Scholar 

  24. Yazdanbakhsh M, Kremsner PG, Van Ree R (2002) Immunology: allergy, parasites, and the hygiene hypothesis. Science (80-.) 296:490–494

    Article  CAS  Google Scholar 

  25. Veldhoen M, Brucklacher-Waldert V (2012) Dietary influences on intestinal immunity. Nat Rev Immunol 12:696–708

    Article  PubMed  CAS  Google Scholar 

  26. Wheeler MA, Rothhammer V, Quintana FJ (2017) Control of immune-mediated pathology via the aryl hydrocarbon receptor. J Biol Chem 292:12383–12389

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Gu Y-Z, Hogenesch JB, Bradfield CA (2000) The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol 40:519–561. https://doi.org/10.1146/annurev.pharmtox.40.1.519

    Article  PubMed  CAS  Google Scholar 

  28. Cella M, Colonna M (2015) Aryl hydrocarbon receptor: linking environment to immunity. Semin Immunol 27:310–314

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Bernink JH, Krabbendam L, Germar K, de Jong E, Gronke K, Kofoed-Nielsen M, Munneke JM, Hazenberg MD, Villaudy J, Buskens CJ, Bemelman WA, Diefenbach A, Blom B, Spits H (2015) Interleukin-12 and -23 control plasticity of Cd127+ group 1 and group 3 innate lymphoid cells in the intestinal Lamina Propria. Immunity 43:146–160. https://doi.org/10.1016/j.immuni.2015.06.019

    Article  PubMed  CAS  Google Scholar 

  30. Kiss EA, Vonarbourg C, Kopfmann S et al (2011) Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science (80-) 334:1561–1565. https://doi.org/10.1126/science.1214914

    Article  CAS  Google Scholar 

  31. Qiu J, Heller JJ, Guo X, Chen ZME, Fish K, Fu YX, Zhou L (2012) The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36:92–104. https://doi.org/10.1016/j.immuni.2011.11.011

    Article  PubMed  CAS  Google Scholar 

  32. Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, Grigorieva EF, Wilhelm C, Veldhoen M (2011) Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147:629–640. https://doi.org/10.1016/j.cell.2011.09.025

    Article  PubMed  CAS  Google Scholar 

  33. Lee JS, Cella M, McDonald KG et al (2012) AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of notch. Nat Immunol 13:144–152. https://doi.org/10.1038/ni.2187

    Article  CAS  Google Scholar 

  34. Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, Omenetti S, Henderson CJ, Wolf CR, Nebert DW, Stockinger B (2017) Feedback control of AHR signalling regulates intestinal immunity. Nature 542:242–245. https://doi.org/10.1038/nature21080

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Zelante T, Iannitti RG, Cunha C, de Luca A, Giovannini G, Pieraccini G, Zecchi R, D’Angelo C, Massi-Benedetti C, Fallarino F, Carvalho A, Puccetti P, Romani L (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39:372–385. https://doi.org/10.1016/j.immuni.2013.08.003

    Article  PubMed  CAS  Google Scholar 

  36. Hall JA, Grainger JR, Spencer SP, Belkaid Y (2011) The role of retinoic acid in tolerance and immunity. Immunity 35:13–22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Duester G (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134:921–931

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Liu Z-M, Wang K-P, Ma J, Guo Zheng S (2015) The role of all-trans retinoic acid in the biology of Foxp3+ regulatory T cells. Cell Mol Immunol 12:553–557. https://doi.org/10.1038/cmi.2014.133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Spencer SP, Wilhelm C, Yang Q et al (2014) Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science (80-) 343:432–437. https://doi.org/10.1126/science.1247606

    Article  CAS  Google Scholar 

  40. Mielke LA, Jones SA, Raverdeau M, Higgs R, Stefanska A, Groom JR, Misiak A, Dungan LS, Sutton CE, Streubel G, Bracken AP, Mills KHG (2013) Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation. J Exp Med 210:1117–1124. https://doi.org/10.1084/jem.20121588

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Van De Pavert SA, Ferreira M, Domingues RG et al (2014) Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity. Nature 508:123–127. https://doi.org/10.1038/nature13158

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Kim MH, Taparowsky EJ, Kim Correspondence CH, Kim CH (2015) Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut. Immunity 43:107–119. https://doi.org/10.1016/j.immuni.2015.06.009

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Murakami M (2011) Lipid mediators in life science. Exp Anim 60:7–20. https://doi.org/10.1538/expanim.60.7

    Article  PubMed  CAS  Google Scholar 

  44. de Jong AJ, Kloppenburg M, Toes RE, Ioan-Facsinay A (2014) Fatty acids, lipid mediators, and T-cell function. Front Immunol 5:483. https://doi.org/10.3389/fimmu.2014.00483

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Theron AJ, Steel HC, Tintinger GR, Gravett CM, Anderson R, Feldman C (2014) Cysteinyl leukotriene receptor-1 antagonists as modulators of innate immune cell function. J Immunol Res 2014:1–16

  46. Cavagnero K, Doherty TA (2017) Cytokine and lipid mediator regulation of group 2 innate lymphoid cells (ILC2s) in human allergic airway disease. J Cytokine Biol 2(2):116. https://doi.org/10.4172/2576-3881.1000116

    Article  PubMed  PubMed Central  Google Scholar 

  47. Doherty TA, Khorram N, Lund S, Mehta AK, Croft M, Broide DH (2013) Lung type 2 innate lymphoid cells express cysteinyl leukotriene receptor 1, which regulates TH2 cytokine production. J Allergy Clin Immunol 132:205–213. https://doi.org/10.1016/j.jaci.2013.03.048

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. von Moltke J, O’Leary CE, Barrett NA, Kanaoka Y, Austen KF, Locksley RM (2017) Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s. J Exp Med 214:27–37. https://doi.org/10.1084/jem.20161274

    Article  CAS  Google Scholar 

  49. Lund SJ, Portillo A, Cavagnero K, Baum RE, Naji LH, Badrani JH, Mehta A, Croft M, Broide DH, Doherty TA (2017) Leukotriene C4 potentiates IL-33-induced group 2 innate lymphoid cell activation and lung inflammation. J Immunol 199:1096–1104. https://doi.org/10.4049/jimmunol.1601569

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Salimi M, Stöger L, Liu W, Go S, Pavord I, Klenerman P, Ogg G, Xue L (2017) Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines. J Allergy Clin Immunol 12:556–562. https://doi.org/10.1016/j.jaci.2016.12.958

    Article  CAS  Google Scholar 

  51. Ricciotti E, Fitzgerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31:986–1000. https://doi.org/10.1161/ATVBAHA.110.207449

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Boyce JA (2007) Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunol Rev 217:168–185

    Article  PubMed  CAS  Google Scholar 

  53. Konya V, Mjösberg J (2016) Lipid mediators as regulators of human ILC2 function in allergic diseases. Immunol Lett 179:36–42. https://doi.org/10.1016/j.imlet.2016.07.006

    Article  PubMed  CAS  Google Scholar 

  54. Xue L, Salimi M, Panse I, Mjösberg JM, McKenzie ANJ, Spits H, Klenerman P, Ogg G (2014) Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol 133:1184–1194.e7. https://doi.org/10.1016/j.jaci.2013.10.056

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Barnig C, Cernadas M, Dutile S, Liu X, Perrella MA, Kazani S, Wechsler ME, Israel E, Levy BD (2013) Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma. Sci Transl Med 5:174ra26. https://doi.org/10.1126/scitranslmed.3004812

    Article  PubMed  CAS  Google Scholar 

  56. Tait Wojno ED, Monticelli LA, Tran SV, Alenghat T, Osborne LC, Thome JJ, Willis C, Budelsky A, Farber DL, Artis D (2015) The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung. Mucosal Immunol 8:1313–1323. https://doi.org/10.1038/mi.2015.21

    Article  PubMed Central  CAS  Google Scholar 

  57. Dorris SL, Peebles RS (2012) PGI2 as a regulator of inflammatory diseases. Mediat Inflamm 2012:926968. https://doi.org/10.1155/2012/926968

    Article  CAS  Google Scholar 

  58. Zhou W, Toki S, Zhang J, Goleniewksa K, Newcomb DC, Cephus JY, Dulek DE, Bloodworth MH, Stier MT, Polosuhkin V, Gangula RD, Mallal SA, Broide DH, Peebles RS Jr (2016) Prostaglandin I2 signaling and inhibition of group 2 innate lymphoid cell responses. Am J Respir Crit Care Med 193:31–42. https://doi.org/10.1164/rccm.201410-1793OC

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Harizi H (2013) The immunobiology of prostanoid receptor signaling in connecting innate and adaptive immunity. Biomed Res Int 2013:683405. https://doi.org/10.1155/2013/683405

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Smith CL, Dickinson P, Forster T, Craigon M, Ross A, Khondoker MR, France R, Ivens A, Lynn DJ, Orme J, Jackson A, Lacaze P, Flanagan KL, Stenson BJ, Ghazal P (2014) Identification of a human neonatal immune-metabolic network associated with bacterial infection. Nat Commun 5. https://doi.org/10.1038/ncomms5649

  61. Duffin R, OConnor RA, Crittenden S et al (2016) Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science (80-) 351:1333–1338. https://doi.org/10.1126/science.aad9903

    Article  CAS  Google Scholar 

  62. Maric J, Ravindran A, Mazzurana L, Björklund ÅK, van Acker A, Rao A, Friberg D, Dahlén SE, Heinemann A, Konya V, Mjösberg J (2017) PGE 2 suppresses human group 2 innate lymphoid cell function. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2017.09.050

  63. Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and Proresolving lipid mediators and pathways. Annu Rev Immunol 25:101–137. https://doi.org/10.1146/annurev.immunol.25.022106.141647

    Article  PubMed  CAS  Google Scholar 

  64. Takabe K, Paugh SW, Milstien S, Spiegel S (2008) “Inside-out” signaling of Sphingosine-1-phosphate: therapeutic targets. Pharmacol Rev 60:181–195. https://doi.org/10.1124/pr.107.07113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Huang Y, Mao K, Chen X, Sun MA, Kawabe T, Li W, Usher N, Zhu J, Urban JF Jr, Paul WE, Germain RN (2018) S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense. Science 359:114–119. https://doi.org/10.1126/science.aam5809

    Article  PubMed  CAS  Google Scholar 

  66. Talbot S, Foster SL, Woolf CJ (2016) Neuroimmunity: physiology and pathology. Annu Rev Immunol 34:421–447. https://doi.org/10.1146/annurev-immunol-041015-055340

    Article  PubMed  CAS  Google Scholar 

  67. Chiu IM, Von Hehn CA, Woolf CJ (2012) Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci 15:1063–1067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Foster SL, Seehus CR, Woolf CJ, Talbot S (2017) Sense and immunity: context-dependent neuro-immune interplay. Front Immunol 8:1463. https://doi.org/10.3389/fimmu.2017.01463

    Article  PubMed  PubMed Central  Google Scholar 

  69. Klose CSN, Mahlakõiv T, Moeller JB, Rankin LC, Flamar AL, Kabata H, Monticelli LA, Moriyama S, Putzel GG, Rakhilin N, Shen X, Kostenis E, König GM, Senda T, Carpenter D, Farber DL, Artis D (2017) The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation. Nature 549:282–286. https://doi.org/10.1038/nature23676

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  70. Wallrapp A, Riesenfeld SJ, Burkett PR, Abdulnour REE, Nyman J, Dionne D, Hofree M, Cuoco MS, Rodman C, Farouq D, Haas BJ, Tickle TL, Trombetta JJ, Baral P, Klose CSN, Mahlakõiv T, Artis D, Rozenblatt-Rosen O, Chiu IM, Levy BD, Kowalczyk MS, Regev A, Kuchroo VK (2017) The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation. Nature 549:351–356. https://doi.org/10.1038/nature24029

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Cardoso V, Chesné J, Ribeiro H, García-Cassani B, Carvalho T, Bouchery T, Shah K, Barbosa-Morais NL, Harris N, Veiga-Fernandes H (2017) Neuronal regulation of type 2 innate lymphoid cells via neuromedin U. Nature 549:277–281. https://doi.org/10.1038/nature23469

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Ganea D, Hooper KM, Kong W (2015) The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases. Acta Physiol (Oxf) 213:442–452. https://doi.org/10.1111/apha.12427

    Article  CAS  Google Scholar 

  73. Talbot S, Abdulnour REE, Burkett PR, Lee S, Cronin SJF, Pascal MA, Laedermann C, Foster SL, Tran JV, Lai N, Chiu IM, Ghasemlou N, DiBiase M, Roberson D, von Hehn C, Agac B, Haworth O, Seki H, Penninger JM, Kuchroo VK, Bean BP, Levy BD, Woolf CJ (2015) Silencing nociceptor neurons reduces allergic airway inflammation. Neuron 87:341–355. https://doi.org/10.1016/j.neuron.2015.06.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Nussbaum JC, Van Dyken SJ, Von Moltke J et al (2013) Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502:245–248. https://doi.org/10.1038/nature12526

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Moriyama S, Brestoff JR, Flamar A-L et al (2018) β2 −adrenergic receptor–mediated negative regulation of group 2 innate lymphoid cell responses. Science (80-) 359:1056–1061. https://doi.org/10.1126/science.aan4829

    Article  CAS  Google Scholar 

  76. Ibiza S, García-Cassani B, Ribeiro H, Carvalho T, Almeida L, Marques R, Misic AM, Bartow-McKenney C, Larson DM, Pavan WJ, Eberl G, Grice EA, Veiga-Fernandes H (2016) Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature 535:440–443. https://doi.org/10.1038/nature18644

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Ashwell JD, Lu FW, Vacchio MS (2000) Glucocorticoids in T cell development and function. Annu Rev Immunol 18:309–345. https://doi.org/10.1146/annurev.immunol.18.1.309

    Article  PubMed  CAS  Google Scholar 

  78. Cain DW, Cidlowski JA (2017) Immune regulation by glucocorticoids. Nat Rev Immunol 17:233–247

    Article  PubMed  CAS  Google Scholar 

  79. Miller WL, Auchus RJ (2011) The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 32:81–151. https://doi.org/10.1210/er.2010-0013

    Article  PubMed  Google Scholar 

  80. Dunn AJ (2000) Cytokine activation of the HPA Axis. Ann N Y Acad Sci 917:608–617. https://doi.org/10.1111/j.1749-6632.2000.tb05426.x

    Article  PubMed  CAS  Google Scholar 

  81. Quatrini L, Wieduwild E, Guia S, Bernat C, Glaichenhaus N, Vivier E, Ugolini S (2017) Host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 innate lymphoid cells. J Exp Med 214(12):3531–3541. https://doi.org/10.1084/jem.20171048

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Kabata H, Moro K, Fukunaga K, Suzuki Y, Miyata J, Masaki K, Betsuyaku T, Koyasu S, Asano K (2013) Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat Commun 4:2675. https://doi.org/10.1038/ncomms3675

    Article  PubMed  CAS  Google Scholar 

  83. Laffont S, Blanquart E, Guery JC (2017) Sex differences in asthma: a key role of androgen-signaling in group 2 innate lymphoid cells. J Immunol 8:1069. https://doi.org/10.3389/fimmu.2017.01069

    Article  Google Scholar 

  84. Laffont S, Blanquart E, Savignac M, Cénac C, Laverny G, Metzger D, Girard JP, Belz GT, Pelletier L, Seillet C, Guéry JC (2017) Androgen signaling negatively controls group 2 innate lymphoid cells. J Exp Med 214:1581–1592. https://doi.org/10.1084/jem.20161807

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Cephus JY, Stier MT, Fuseini H, Yung JA, Toki S, Bloodworth MH, Zhou W, Goleniewska K, Zhang J, Garon SL, Hamilton RG, Poloshukin VV, Boyd KL, Peebles RS Jr, Newcomb DC (2017) Testosterone attenuates group 2 innate lymphoid cell-mediated airway inflammation. Cell Rep 21:2487–2499. https://doi.org/10.1016/j.celrep.2017.10.110

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Bartemes K, Chen CC, Iijima K, Drake L, Kita H (2018) IL-33-responsive group 2 innate lymphoid cells are regulated by female sex hormones in the uterus. J Immunol 200(1):229–236. https://doi.org/10.4049/jimmunol.1602085

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the NRW-Return program of the Ministry for Science and Education of North-Rhine-Westphalia and the Deutsche Forschungsgemeinschaft DFG [program grant from the DFG (SPP1937)]. CW is a member of the DFG Excellence Cluster Immunosensation.

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  1. Unit for Immunopathology, Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany

    Fotios Karagiannis & Christoph Wilhelm

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  2. Christoph Wilhelm
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All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

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Correspondence to Christoph Wilhelm.

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This article is a contribution to the special issue on Innate Lymphoid Cells in Inflammation and Immunity - Guest Editors: Jan-Eric Turner and Georg Gasteiger

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Karagiannis, F., Wilhelm, C. Innate lymphoid cells—key immune integrators of overall body homeostasis. Semin Immunopathol 40, 319–330 (2018). https://doi.org/10.1007/s00281-018-0684-y

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