Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology.

Abstract

UV irradiation of mice causes a systemic immune alteration that can be detected either by suppression of the immunologic rejection of UV-induced tumors, or by suppression of contact hypersensitivity (CHS). Suppression of these two immunologic responses has similar photobiologic characteristics and in both cases is associated with the generation of antigen-specific suppressor T cells. To identify whether a specific photoreceptor for this effect exists, the relative wavelength effectiveness (action spectrum) was determined for the UV-induced suppression of CHS. Narrow bands of UV (half bandwidth 3 nm) were used at 10 wavelengths from 250 to 320 nm to obtain dose-response curves. Irradiation with each of these bands of UV caused dose-dependent immunosuppression of CHS, but with differing effectiveness. Immunosuppression was clearly separable from the generation of gross skin damage and inflammation. Further, immunosuppression by the most effective wavelength (270 nm) was associated with the generation of antigen-specific suppressor cells. The action spectrum derived from the dose-response curves has a maximum between 260 and 270 nm, a shoulder at 280-290 nm, and declines steadily to approximately 3% of maximum at 320 nm. The finding of such a clearly defined wavelength dependence implies the presence of a specific photoreceptor for this effect. Removing the stratum corneum by tape stripping before UV irradiation prevented the suppression of CHS using 254-nm radiation, suggesting the photoreceptor is superficially located in the skin. A number of epidermal compounds with absorption spectra similar to the action spectrum are discussed and evaluated with respect to their potential for being the photoreceptor. Based on (a) the close fit of its absorption spectrum to the action spectrum, (b) its superficial location in the stratum corneum, and (c) its photochemical properties, the hypothesis is advanced that the photoreceptor for systemic UV-induced immunosuppression of contact hypersensitivity may be urocanic acid. As such, it may also play a role in UV-induced carcinogenesis via the production of tumor-specific suppressor cells.

A single dose of UV radiation suppresses delayed type hypersensitivity responses to alloantigens and prolongs heart allograft survival in mice

“…The current studies have shown that UV irradiation may be usefui not oniy for pretreatment of donor tissue but also for immune suppression of graft recipients. UV radiation-induced immunosuppression in vivo is initiated by an interaction between UV and a superficial photoreceptor in skin, tentatively identified as urocanic acid, which photoisomerizes on UV irradiation (26). Recent supportive evidence for this hypothesis has been pre-scntcd indicating that systemic administration of the UV-irradiated form of urocanic acid can initiate, in the absence of UV suppression of a DTH response (27) and the formation of an antigen-presenting cell defect in dendritic antigen presenting cells ofthe spleen (19).…”

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

“…As can be seen in Figure 6, P2X 7 receptor signaling is not required for UV-induced IL-33 in the skin because both groups of mice showed an increase in IL-33 expression. A number of other soluble factors are released within the skin after exposure to inflammatory doses of UV, including cis-urocanic acid (cis-UCA) 52 and the oxidized membrane lipid PAF. 53 To determine whether cis-UCA ( Figure 6F) or PAF ( Figure 6G) could directly induce IL-33 expression in fibroblasts, we incubated MEFs with each of these factors for 1 hour or 4 hours.…”

Production of suppressor factors induced by ultraviolet irradiation or cis‐urocanic acid requires Lyt‐2+ lymphocytes

“…UCA has been suggested as the photoreceptor in the UVR-induced immunosuppressive process (6), and several papers have demonstrated that the cis isomer of UCA can alter a number of immunological phenomena (5,(7)(8)(9)(10). The exact mechanism of action of UCA, however, has yet to be determined.…”

“…a.y-UCA is derived by UV irradiation from trans-\JC\, a natural skin component, and has only recently been implicated in the immunosuppressive action of UV radiation (UVR). De Fabo and Noonan first suggested that UCA was the unique photoreceptor in skin (6), and further recent publications have elucidated its role in immunosuppression (7)(8)(9)(10).…”