The alternative complement pathway seems to be a UVA sensor that leads to systemic immunosuppression.
UV wavebands in sunlight are immunomodulatory. About half the amount of UVA within a minimum erythemal dose of sunlight is systemically immunosuppressive, whereas higher doses protect from UVB immunosuppression in mice. We have earlier shown that these responses to UVA are genetically restricted, as they occur in C57BL/6 but not in Balb/c mice. We used gene set enrichment analysis of microarray data and real-time reverse transcriptase (RT)-PCR confirmation to determine the molecular mechanisms associated with UVA immunomodulation. We found upregulation of mRNA for the alternative complement pathway. The core-enriched genes complement component 3, properdin, and complement factor B were all activated by the immunosuppressive dose of UVA only in UVA-responsive C57BL/6 but not in unresponsive BALB/c mice. This therefore matched the genetic restriction and dose responsiveness of UVA immunosuppression. The immune-protective higher UVA dose prevented UVB from downregulating chemokine receptor 7 and IL-12B, and decreased IL-10, supporting the earlier identification of IL-12 and IL-10 in high-dose UVA protection from UVB immunosuppression. Our study has identified activation of the alternative complement pathway as a trigger of UVA-induced systemic immunosuppression and suggests that this pathway is likely to be an important sensor of UVA-induced damage to the skin.
Stapelberg
Michael P F
MP
Discipline of Dermatology, Bosch Institute, Sydney Cancer Centre, at the University of Sydney, New South Wales, Australia.
Williams
Rohan B H
RB
Byrne
Scott N
SN
Halliday
Gary M
GM
D000818:Animals; D003170:Complement Pathway, Alternative / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015870:Gene Expression / Q000276:immunology / Q000528:radiation effects; D007108:Immune Tolerance / Q000276:immunology* / Q000528:radiation effects*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D054400:Receptors, CCR7 / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000528:radiation effects*; D013472:Sunlight; D014466:Ultraviolet Rays
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D016753:Interleukin-10; D018664:Interleukin-12