Mechanism involved in the systemic suppression of antigen-presenting cell function by UV irradiation. Keratinocyte-derived IL-10 modulates antigen-presenting cell function of splenic adherent cells.
Exposure to UV radiation suppresses tumor rejection and delayed-in-time hypersensitivity reactions and depresses splenic APC function. Because almost all of the UV radiation is absorbed in the upper layers of the skin, it appears unlikely the direct irradiation of APC can account for the impaired ability of splenic adherent cells to present Ag after total-body UV exposure. Because UV-irradiated keratinocytes release IL-10, and in light of the well-documented effects of IL-10 on Ag presentation, we tested the hypothesis that keratinocyte-derived IL-10 is responsible for the systemic impairment of APC function following UV exposure. Injecting supernatants from UV-irradiated keratinocytes suppressed the ability of splenic adherent cells to present Ag. Treating the supernatants with anti-IL-10 mAb neutralized the suppressive effect. Similarly, when splenic adherent cells were isolated from mice exposed to UV radiation, APC function was suppressed. Injecting the UV-irradiated animals with anti-IL-10 restored APC function. In addition, spleen cells from UV-irradiated mice did not efficiently present Ag to Th1 clones, and injecting anti-IL-10 after UV exposure restored APC function. The reverse was observed when spleen cells from UV-irradiated mice were used to present Ag to Th2 clones; in which case, UV exposure enhances APC function, and anti-IL-10 reverses this effect. These findings suggest that UV-induced, keratinocyte-derived IL-10 can modulate splenic APC function.
Ullrich
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Department of Immunology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D005260:Female; D016753:Interleukin-10 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015603:Keratinocytes / Q000502:physiology / Q000528:radiation effects*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014466:Ultraviolet Rays
D007376:Interleukin-2; D016753:Interleukin-10