Skip to main content
Log in

Lipids in ultraviolet radiation-induced immune modulation

  • Perspective
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Ultraviolet (UV) radiation-mediated immune suppression is a key mechanism conferring both detrimental and beneficial impacts of sun exposure on human health. Suppression of anti-tumour responses promotes the development and progression of UV-induced skin cancers. In contrast, suppression of dysregulated immune responses facilitate the therapeutic success of phototherapy treatment for skin disorders and is postulated to be responsible for UV protection from autoimmune diseases. While some of the molecular and cellular mechanisms underlying UV-suppression of the immune system are known, a relatively unexplored area is immunomodulatory lipids. Cutaneous UV exposure changes lipids both locally in the skin, increasing platelet-activating factor (PAF) production and decreasing free triglyceride levels, and systemically reducing adipose tissue mass. There is growing recognition that bioactive lipids and lipid metabolism directly affect immune cell phenotype and function. Manipulation of immunomodulatory lipid pathways are effective strategies in modifying systemic immune responses. Indeed, the PAF pathway is a key initiator of UV-induced immune suppression and antagonism of PAF-receptors restores immune function and reduces skin cancer development in mice. This review focuses on the known effects of UV on lipids and proposes how this may in turn be involved in the modulation of the immune system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. P. H. Hart, et al., Exposure to Ultraviolet Radiation in the Modulation of Human Diseases, Annu. Rev. Pathol., 2019, 14, 55–81.

    CAS  PubMed  Google Scholar 

  2. D. S. Rigel, Cutaneous ultraviolet exposure and its relationship to the development of skin cancer, J. Am. Acad. Dermatol., 2008, 58(5 Suppl. 2), S129–S132.

    PubMed  Google Scholar 

  3. E. D. Pleasance, et al., A comprehensive catalogue of somatic mutations from a human cancer genome, Nature, 2010, 463(7278), 191–196.

    CAS  PubMed  Google Scholar 

  4. E. Waubant, et al., Environmental and genetic risk factors for MS: an integrated review, Ann. Clin. Transl. Neurol., 2019, 6(9), 1905–1922.

    Google Scholar 

  5. M. L. Kripke, et al., Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice, Proc. Natl. Acad. Sci. U. S. A., 1992, 89(16), 7516–7520.

    CAS  PubMed  Google Scholar 

  6. J. M. Kuchel, R. S. Barnetson and G. M. Halliday, Cyclobutane pyrimidine dimer formation is a molecular trigger for solar-simulated ultraviolet radiation-induced suppression of memory immunity in humans, Photochem. Photobiol. Sci., 2005, 4(8), 577–582.

    CAS  PubMed  Google Scholar 

  7. P. Wolf, et al., Immune protection factors of chemical sunscreens measured in the local contact hypersensitivity model in humans, J. Invest. Dermatol., 2003, 121(5), 1080–1087.

    CAS  PubMed  Google Scholar 

  8. D. Yarosh, et al., Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group, Lancet, 2001, 357(9260), 926–929.

    CAS  Google Scholar 

  9. E. Damiani and S. E. Ullrich, Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer, Prog. Lipid Res., 2016, 63, 14–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. A. Fukunaga, et al., Langerhans cells serve as immunoregulatory cells by activating NKT cells, J. Immunol., 2010, 185(8), 4633–4640.

    CAS  PubMed  Google Scholar 

  11. A. M. Moodycliffe, et al., Immune suppression and skin cancer development: regulation by NKT cells, Nat. Immunol., 2000, 1(6), 521–525.

    CAS  PubMed  Google Scholar 

  12. S. N. Byrne, A. Y. Limon-Flores and S. E. Ullrich, Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression, J. Immunol., 2008, 180(7), 4648–4655.

  13. S. N. Sarchio, et al., Pharmacologically antagonizing the CXCR4-CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer, J. Invest. Dermatol., 2014, 134(4), 1091–1100.

    CAS  PubMed  Google Scholar 

  14. A. Maeda, et al., Phenotypic and functional characterization of ultraviolet radiation-induced regulatory T cells, J. Immunol., 2008, 180(5), 3065–3071.

    CAS  PubMed  Google Scholar 

  15. S. N. Byrne and G. M. Halliday, B cells activated in lymph nodes in response to ultraviolet irradiation or by interleukin-10 inhibit dendritic cell induction of immunity, J. Invest. Dermatol., 2005, 124(3), 570–578.

    CAS  PubMed  Google Scholar 

  16. S. N. Byrne, J. Ahmed and G. M. Halliday, Ultraviolet B but not A radiation activates suppressor B cells in draining lymph nodes, Photochem. Photobiol., 2005, 81(6), 1366–1370.

  17. K. Loser, et al., Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells, Nat. Med., 2006, 12(12), 1372–1379.

    CAS  PubMed  Google Scholar 

  18. L. F. Kok, et al., B cells are required for sunlight protection of mice from a CNS-targeted autoimmune attack, J. Autoimmun., 2016, 73, 10–23.

    CAS  PubMed  Google Scholar 

  19. L. F. Kok, et al., B cell-targeted immunotherapy limits tumor growth, enhances survival and prevents lymph node metastasis of UV-induced keratinocyte cancers in mice, J. Invest. Dermatol., 2020, DOI: 10.1016/j.jid.2019.12.018.

  20. N. J. Hawkshaw, et al., UV radiation recruits CD4(+)GATA3 (+) and CD8(+)GATA3(+) T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo, Clin. Transl. Immunol., 2020, 9(4), e01104.

  21. R. D. Michalek, et al., Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+T cell subsets, J. Immunol., 2011, 186(6), 3299–3303.

    CAS  PubMed  Google Scholar 

  22. E. L. Pearce, et al., Enhancing CD8 T-cell memory by modulating fatty acid metabolism, Nature, 2009, 460(7251), 103–107.

    CAS  PubMed  Google Scholar 

  23. Y. Shinjo, et al., Lysophosphatidylserine suppresses IL-2 production in CD4 T cells through LPS3/GPR174, Biochem. Biophys. Res. Commun., 2017, 494(1–2), 332–338.

  24. M. J. Barnes and J. G. Cyster, Lysophosphatidylserine suppression of T-cell activation via GPR174 requires Galphas proteins, Immunol. Cell Biol., 2018, 96(4), 439–445.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. M. M. Mathews-Roth and N. I. Krinsky, Effect of dietary fat level on UV-B induced skin tumors, and anti-tumor action of beta-carotene, Photochem. Photobiol., 1984, 40(5), 671–673.

    CAS  PubMed  Google Scholar 

  26. V. E. Reeve, et al., Effect of dietary lipid on UV light carcino-genesis in the hairless mouse, Photochem. Photobiol., 1988, 48(5), 689–696.

    CAS  Google Scholar 

  27. H. S. Black and L. E. Rhodes, Potential Benefits of Omega-3 Fatty Acids in Non-Melanoma Skin Cancer, J. Clin. Med., 2016, 5(2), 23.

    PubMed Central  Google Scholar 

  28. E. J. Kim, et al., UV decreases the synthesis of free fatty acids and triglycerides in the epidermis of human skin in vivo, contributing to development of skin photoaging, J. Dermatol. Sci., 2010, 57(1), 19–26.

    CAS  PubMed  Google Scholar 

  29. E. J. Kim, et al., UV modulation of subcutaneous fat metabolism, J. Invest. Dermatol., 2011, 131(8), 1720–1726.

    CAS  PubMed  Google Scholar 

  30. S. Geldenhuys, et al., Ultraviolet radiation suppresses obesity and symptoms of metabolic syndrome independently of vitamin D in mice fed a high-fat diet, Diabetes, 2014, 63(11), 3759–3769.

    CAS  PubMed  Google Scholar 

  31. G. K. Dhamrait, et al., Characterising nitric oxide-mediated metabolic benefits of low-dose ultraviolet radiation in the mouse: a focus on brown adipose tissue, Diabetologia, 2020, 63(1), 179–193.

    CAS  PubMed  Google Scholar 

  32. A. L. Ferguson, et al., Exposure to solar ultraviolet radiation limits diet-induced weight gain, increases liver triglycerides and prevents the early signs of cardiovascular disease in mice, Nutr. Metab. Cardiovasc. Dis., 2019, 29(6), 633–638.

    CAS  PubMed  Google Scholar 

  33. N. Fleury, et al., Sub-erythemal ultraviolet radiation reduces metabolic dysfunction in already overweight mice, J. Endocrinol., 2017, 233(1), 81–92.

    CAS  PubMed  Google Scholar 

  34. S. Teng, et al., Regular exposure to non-burning ultraviolet radiation reduces signs of non-alcoholic fatty liver disease in mature adult mice fed a high fat diet: results of a pilot study, BMC Res. Notes, 2019, 12(1), 78.

    PubMed  PubMed Central  Google Scholar 

  35. K. M. Miller, et al., Are low sun exposure and/or vitamin D risk factors for type 1 diabetes?, Photochem. Photobiol. Sci., 2017, 16(3), 381–398.

    CAS  PubMed  Google Scholar 

  36. C. Colas, et al., Insulin secretion and plasma 1,25-(OH)2D after UV-B irradiation in healthy adults, Horm. Metab. Res., 1989, 21(3), 154–155.

    CAS  Google Scholar 

  37. J. H. Ohn, et al., Unprotected daily sun exposure is differently associated with central adiposity and beta-cell dysfunction by gender: the Korean National Health and Nutrition Examination Survey (KNHANES) V, Environ. Res., 2014, 133, 253–259.

    CAS  PubMed  Google Scholar 

  38. S. W. Lin, et al., Prospective study of ultraviolet radiation exposure and mortality risk in the United States, Am. J. Epidemiol., 2013, 178(4), 521–533.

    PubMed  Google Scholar 

  39. D. Liu, et al., UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase, J. Invest. Dermatol., 2014, 134(7), 1839–1846.

    CAS  PubMed  Google Scholar 

  40. P. Wolf, et al., Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis, Am. J. Pathol., 2006, 169(3), 795–805.

  41. Y. Matsumura, et al., A role for inflammatory mediators in the induction of immunoregulatory B cells, J. Immunol., 2006, 177(7), 4810–4817.

    CAS  PubMed  Google Scholar 

  42. M. Ferracini, et al., Topical photodynamic therapy induces systemic immunosuppression via generation of platelet-activating factor receptor ligands, J. Invest. Dermatol., 2015, 135(1), 321–323.

  43. J. P. Walterscheid, S. E. Ullrich and D. X. Nghiem, Platelet-activating Factor, a Molecular Sensor for Cellular Damage, Activates Systemic Immune Suppression, J. Exp. Med., 2002, 195(2), 171–179.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. C. S. Sreevidya, et al., Inhibition of photocarcinogenesis by platelet-activating factor or serotonin receptor antagonists, Cancer Res., 2008, 68(10), 3978–3984.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. R. P. Sahu, et al., The environmental stressor ultraviolet B radiation inhibits murine antitumor immunity through its ability to generate platelet-activating factor agonists, Carcinogenesis, 2012, 33(7), 1360–1367.

    CAS  PubMed  Google Scholar 

  46. J. B. Travers, et al., Acute ethanol exposure augments low dose UVB-mediated systemic immunosuppression via enhanced production of Platelet-activating factor receptor agonists, J. Invest. Dermatol., 2019, 139(7), 1619–1622.

    CAS  PubMed  Google Scholar 

  47. A. Jensen, et al., Intake of alcohol may modify the risk for non-melanoma skin cancer: results of a large Danish prospective cohort study, J. Invest. Dermatol., 2012, 132(12), 2718–2726.

    CAS  PubMed  Google Scholar 

  48. G. J. van der Windt, et al., Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development, Immunity, 2012, 36(1), 68–78.

    Google Scholar 

  49. G. J. van der Windt, et al., CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability, Proc. Natl. Acad. Sci. U. S. A., 2013, 110(35), 14336–14341.

    PubMed  Google Scholar 

  50. S. Rana, et al., Ultraviolet B suppresses immunity by inhibiting effector and memory T cells, Am. J. Pathol., 2008, 172(4), 993–1004.

    PubMed  Google Scholar 

  51. M. J. Barnes, et al., The lysophosphatidylserine receptor GPR174 constrains regulatory T cell development and function, J. Exp. Med., 2015, 212(7), 1011–1020.

    CAS  Google Scholar 

  52. D. Qiu, et al., Gpr174-deficient regulatory T cells decrease cytokine storm in septic mice, Cell Death Dis., 2019, 10(3), 233.

    PubMed  PubMed Central  Google Scholar 

  53. S. R. Schwab, et al., Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients, Science, 2005, 309(5741), 1735–1739.

    CAS  PubMed  Google Scholar 

  54. I. Moreno-Torres, et al., Immunophenotype and Transcriptome Profile of Patients With Multiple Sclerosis Treated With Fingolimod: Setting Up a Model for Prediction of Response in a 2-Year Translational Study, Front. Immunol., 2018, 9, 1693.

    Google Scholar 

  55. A. M. Farrell, et al., UVB irradiation up-regulates serine palmitoyltransferase in cultured human keratinocytes, J. Lipid Res., 1998, 39(10), 2031–2038.

    CAS  PubMed  Google Scholar 

  56. L. Russo and C. N. Lumeng, Properties and functions of adipose tissue macrophages in obesity, Immunology, 2018, 155(4), 407–417.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. L. Boutens, et al., Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses, Diabetologia, 2018, 61(4), 942–953.

    CAS  PubMed  Google Scholar 

  58. A. Kennedy, et al., Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications, J. Nutr., 2009, 139(1), 1–4.

    CAS  PubMed  Google Scholar 

  59. M. J. Song, et al., Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes, Biochem. Biophys. Res. Commun., 2006, 346(3), 739–745.

    CAS  PubMed  Google Scholar 

  60. T. Suganami, et al., Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages, Arterioscler., Thromb., Vasc. Biol., 2007, 27(1), 84–91.

    CAS  Google Scholar 

  61. M. J. Hubler and A. J. Kennedy, Role of lipids in the metabolism and activation of immune cells, J. Nutr. Biochem., 2016, 34, 1–7.

    CAS  PubMed  Google Scholar 

  62. T. Suganami, et al., Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation, Biochem. Biophys. Res. Commun., 2007, 354(1), 45–49.

    CAS  Google Scholar 

  63. W. Lewis, et al., Regulation of ultraviolet radiation induced cutaneous photoimmunosuppression by toll-like receptor-4, Arch. Biochem. Biophys., 2011, 508(2), 171–177.

    CAS  PubMed  Google Scholar 

  64. E. Oliver, et al., Docosahexaenoic acid attenuates macro-phage-induced inflammation and improves insulin sensitivity in adipocytes-specific differential effects between LC n-3 PUFA, J. Nutr. Biochem., 2012, 23(9), 1192–1200.

    CAS  PubMed  Google Scholar 

  65. H. Wang, et al., Omega-3 polyunsaturated fatty acids affect lipopolysaccharide-induced maturation of dendritic cells through mitogen-activated protein kinases p38, Nutrition, 2007, 23(6), 474–482.

    PubMed  Google Scholar 

  66. E. Draper, et al., Conjugated linoleic acid suppresses dendritic cell activation and subsequent Th17 responses, J. Nutr. Biochem., 2014, 25(7), 741–749.

    CAS  PubMed  Google Scholar 

  67. A. Storey, et al., Conjugated linoleic acids modulate UVR-induced IL-8 and PGE2 in human skin cells: potential of CLA isomers in nutritional photoprotection, Carcinogenesis, 2007, 28(6), 1329–1333.

    CAS  Google Scholar 

  68. L. E. Rhodes, et al., Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in skin and increases the threshold to provocation of polymorphic light eruption, J. Invest. Dermatol., 1995, 105(4), 532–535.

    CAS  PubMed  Google Scholar 

  69. R. M. Moison and G. M. Beijersbergen Van Henegouwen, Dietary eicosapentaenoic acid prevents systemic immuno-suppression in mice induced by UVB radiation, Radiat. Res., 2001, 156(1), 36–44.

    CAS  PubMed  Google Scholar 

  70. R. M. Moison, D. P. Steenvoorden and G. M. Beijersbergen van Henegouwen, Topically applied eicosapentaenoic acid protects against local immunosuppression induced by UVB irradiation, cis-urocanic acid and thymidine dinucleotides, Photochem. Photobiol., 2001, 73(1), 64–70.

    CAS  PubMed  Google Scholar 

  71. S. M. Pilkington, et al., Impact of EPA ingestion on COX-and LOX-mediated eicosanoid synthesis in skin with and without a pro-inflammatory UVR challenge–report of a randomised controlled study in humans, Mol. Nutr. Food Res., 2014, 58(3), 580–590.

    CAS  Google Scholar 

  72. S. M. Pilkington, et al., Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR-exposed human skin: a randomised controlled study, Exp. Dermatol., 2016, 25(12), 962–968.

    CAS  PubMed  Google Scholar 

  73. R. Correa-Oliveira, et al., Regulation of immune cell function by short-chain fatty acids, Clin. Transl. Immunol., 2016, 5(4), e73.

  74. B. Memari, et al., Endocrine aryl hydrocarbon receptor signaling is induced by moderate cutaneous exposure to ultraviolet light, Sci. Rep., 2019, 9(1), 8486.

    PubMed  PubMed Central  Google Scholar 

  75. E. S. Bosman, et al., Skin Exposure to Narrow Band Ultraviolet (UVB) Light Modulates the Human Intestinal Microbiome, Front. Microbiol., 2019, 10, 2410.

    PubMed  Google Scholar 

  76. S. Ghaly, N. O. Kaakoush and P. H. Hart, Effects of UVR exposure on the gut microbiota of mice and humans, Photochem. Photobiol. Sci., 2020, 19(1), 20–28.

    CAS  PubMed  Google Scholar 

  77. M. A. Cox, et al., Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines, World J. Gastroenterol., 2009, 15(44), 5549–5557.

    CAS  Google Scholar 

  78. P. M. Smith, et al., The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis, Science, 2013, 341(6145), 569–573.

    CAS  PubMed  Google Scholar 

  79. A. Schwarz, A. Bruhs and T. Schwarz, The Short-Chain Fatty Acid Sodium Butyrate Functions as a Regulator of the Skin Immune System, J. Invest. Dermatol., 2017, 137(4), 855–864.

    CAS  PubMed  Google Scholar 

  80. A. Krejner, et al., Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in psoriatic skin can be restored by topical application of sodium butyrate, Arch. Dermatol. Res., 2018, 310(9), 751–758.

    CAS  PubMed  Google Scholar 

  81. V. Patra, et al., Skin Microbiome Modulates the Effect of Ultraviolet Radiation on Cellular Response and Immune Function, iScience, 2019, 15, 211–222.

    CAS  PubMed  Google Scholar 

  82. S. Sethi and E. Brietzke, Recent advances in lipidomics: Analytical and clinical perspectives, Prostaglandins Other Lipid Mediators, 2017, 128–129, 8–16.

    PubMed  Google Scholar 

  83. Z. Yu, et al., Global lipidomics reveals two plasma lipids as novel biomarkers for the detection of squamous cell lung cancer: A pilot study, Oncol. Lett., 2018, 16(1), 761–768.

    PubMed  Google Scholar 

  84. X. Chen, et al., Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions, Oncotarget, 2016, 7(24), 36622–36631.

    PubMed  Google Scholar 

  85. A. Aquino, et al., Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients, Front. Psychiatry, 2018, 9, 209.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Scott N. Byrne.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tse, B.C.Y., Byrne, S.N. Lipids in ultraviolet radiation-induced immune modulation. Photochem Photobiol Sci 19, 870–878 (2020). https://doi.org/10.1039/d0pp00146e

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/d0pp00146e

Navigation