Mucosal-associated invariant T (MAIT) cells mediate IFN-I dependent immunosuppression in UV light-exposed skin: implications for lupus photosensitivity 2796

Abstract Description Skin exposure to ultraviolet B (UVB) light causes cell death and DNA damage that induces immunosuppression in healthy skin. MAIT cells are functionally diverse innate-like lymphocytes that conventionally respond to microbial-derived antigens but can be activated by cytokines including IFN-I, independent of TCR stimulus. The role of MAIT cells in UVB-induced immunosuppression is unknown. Using MAIT cell specific tetramer, we found that low-dose chronic UVB exposure expands MAIT cells in healthy C57/Bl6 skin. MAIT expansion was paralleled by induction of MAIT-associated tissue repair genes (Tgfb1, Cxcl16) and Treg proliferation and increased expression of Cxcl16 receptor CXCR6 that is important for skin retention of Treg. In MAIT cell-deficient skin (B6.Mr1-/-), UVB failed to induce the expression of tissue repair genes or expand Treg, confirming that UVB-induced Treg expansion in the skin is MAIT cell-dependent. Neither MAIT cells nor Treg expanded in mice lacking the IFN-I receptor (B6.IFNAR-/-) following chronic UVB, suggesting the MAIT-Treg axis in healthy skin is IFN-I driven. The skin of MRL-lpr lupus prone mice harbored ∼10-fold fewer skin MAIT cells than healthy B6 skin. UVB light failed to stimulate MAIT or Treg expansion in lupus-like (MRL-lpr) skin. These findings highlight a critical IFN-I driven MAIT-Treg axis in UVB-induced immunosuppression and suggest that restoring MAIT cells in lupus-prone skin may mitigate photosensitivity and promote tissue repair. Funding Sources T32 AI007363 NIAMS R01AR080641 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)