Hapten-specific tolerance induced by acute, low-dose ultraviolet B radiation of skin requires mast cell degranulation

The deleterious effects of ultraviolet B radiation (UVR) on cutaneous immun ity are mediated in part by cytokines released from cutaneous cells followi ng radiation exposure. On the one hand, TNF-alpha has been advocated as the primary mediator of failed contact hypersensitivity induction, and, on the other hand, IL-10 has been held responsible for tolerance. While keratinoc ytes exposed to UVR have been found to produce both TNF-alpha and IL-10, th ere is reason to question whether these major cellular constituents of the epidermis are the relevant source of immunomodulatory cytokines after UVR. Dermal mast cells also produce TNF-alpha and IL-10, and we have recently re ported that mast cell-derived TNF-alpha is required for UVR-induced impairm ent of CH induction. In this study, we have examined whether mast cells are also a relevant source of IL-10 in UVR-dependent tolerance. We found that (a) UVR fails to induce tolerance in mast cell-deficient mice, and (b) that tolerance occurs if mast cells are triggered to degranulate after ligation of the IgE receptor. Both types of tolerance were neutralized with anti-IL -10 antibodies, are hapten specific, and are associated with regulatory lym phoid cells. We conclude that mast cells are required in UVR-induced tolera nce and may be one of the major sources of IL-10 that mediates the toleranc e induced by acute, low-dose UVR.