MyD88 Plays an Important Role in UVB-Induced Suppression of Dendritic Cell Activity, T Cell Function, and Cutaneous Immune Response.

Ultraviolet B (UVB) radiation triggers DNA damage and immune suppression, establishing conditions favorable for skin carcinogenesis. Previous studies have shown that a downstream adaptor for Toll-like receptors (TLRs), myeloid differentiation primary response 88 (MyD88), plays a role in UVB-induced DNA damage and immunosuppression. However, specific mechanisms for the effects on dendritic cells and T cells remain poorly understood. The objective of this study is to determine the role of MyD88 and TIR-domain-containing adaptor inducing interferon-β (TRIF), another key TLR downstream adaptor, in UVB-induced suppression of dendritic cell activity and T cell function. MyD88-/-, Trif-/-, and wild-type (WT) mice were evaluated for UVB-induced effects on dendritic cell, T cells, and contact hypersensitivity responses in skin. MyD88-/- mice exhibited significant resistance to UVB-induced immune suppression, compared to Trif-/- mice and wild-type controls. The MyD88 deficiency significantly reduced UVB-induced Treg cells that were CD4+CD25+Foxp3+ and produced interleukin (IL)-10. Moreover, it significantly inhibited the UVB-induced suppression of IL-12/IL-23 producing CD11c+ dendritic cells. Further experiments confirmed that MyD88 conditional knockout (MyD88fl/flXCD11c.Cre) mice were protected against UVB-induced immune suppression. Dendritic cells from MyD88 genomic or conditional knockout mice were resistant to UVB-induced reduction of major histocompatibility complex (MHC) class II antigens. These findings show that MyD88 plays a key role in UVB-induced immune suppression. The deficiency in the MyD88 gene inhibits UVB-induced suppression of CD11c+ dendritic cell (DC) activity and reduces UVB-induced development of Treg cells. Our studies demonstrate a new mechanism for MyD88-mediated regulation of UVB-induced immune suppression.