Ultraviolet B-Induced Suppression of Immune Responses in Interleukin-4–/– Mice: Relationship to Dermal Mast Cells

Abstract

Ultraviolet B radiation is immunosuppressive by multiple mechanisms. In interleukin-4-/- mice, ultraviolet B radiation was not able to suppress delayed-type hypersensitivity or contact hypersensitivity responses when the sensitizing antigen was applied to nonirradiated sites. In contrast, ultraviolet B significantly suppressed contact hypersensitivity responses to haptens applied to irradiated sites in interleukin-4-/- mice. In mast cell depleted Wf/Wf mice, ultraviolet B radiation also significantly suppressed contact hypersensitivity responses to sensitizing antigens applied to irradiated but not to unirradiated sites. In both interleukin-4-/- mice and Wf/Wf mice, the mast cell product, histamine, was immunosuppressive implicating mast cells as the dysfunctional cell in interleukin-4-/- mice. The prevalence of dermal mast cells was similar in wild-type and interleukin-4-/- mice. Dermal mast cells of interleukin-4-/- mice, however, express very low levels of c-kit and did not significantly degranulate in response to ultraviolet B. Ultraviolet radiation induced significant and similar levels of serum interleukin-10 in wild-type and interleukin-4-/- mice. We conclude that interleukin-4 indirectly affects ultraviolet B suppression of contact hypersensitivity and delayed-type hypersensitivity responses to sensitizing antigens applied at sites other than those irradiated by providing a critical differentiative signal for dermal mast cells. This study further emphasizes the central role of mast cells in the initial processes by which ultraviolet B radiation is immunomodulatory for immune responses to sensitizing antigens applied to nonirradiated sites.

Ultraviolet B irradiation selectively increases the production of interleukin-8 in human cord blood-derived mast cells

“…Although UVB affects predominantly the epidermis, studies indicate that a proportion of UVB light (~15%) penetrates into the reticular dermis [21] where mast cells are located [22]. There is sufficient evidence implicating mast cells in UVB-induced acute inflammation and immune modulation [23] but their exact roles are not understood fully.…”

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

“…8 Unfortunately, the exact mechanism by which UV modulates inflammation and immunity is not completely understood, even though understanding these events could lead to the design of novel immune-modulating treatment regimes. UV-induced DNA damage, 9 together with the production of oxidized lipids 10 and the release of immune-modulating cytokines (particularly prostaglandin E 2 , IL-4, and IL-10 11,12 ) play important roles. The downstream cellular targets of these UV-induced inflammatory mediators include dendritic cells, 13 dermal mast cells, 12 as well as regulatory T 14 and B cells.…”

“…UV-induced DNA damage, 9 together with the production of oxidized lipids 10 and the release of immune-modulating cytokines (particularly prostaglandin E 2 , IL-4, and IL-10 11,12 ) play important roles. The downstream cellular targets of these UV-induced inflammatory mediators include dendritic cells, 13 dermal mast cells, 12 as well as regulatory T 14 and B cells. 15,16 Consequently, UV is broadly immunosuppressive, having the capacity to suppress the induction and effector phases of CD8 -T-cell responses, development of immunological memory, 17 Th1-driven 18 and Th2-driven immunity, 19 as well as antibody-mediated immune responses.…”

Photoimmunology and Multiple Sclerosis

“…UVB-induced IL-4 is also likely to be a critical differentiation signal for dermal mast cells because degranulation is defective in IL-4-deficient mice exposed to UVB. This defect has a significant impact on downstream UVB-induced immune suppression (Hart et al 2000).…”