Merkel cells attenuate autoantigen-specific T-cell-driven skin inflammation in mice associated with reduced neutrophil recruitment.

Cutaneous lupus erythematosus is a lymphocytic interface dermatitis condition that affects the skin and mucosa. Many patients experience photosensitivity and itch. Recent work has demonstrated that Merkel cells in the skin are important for itch responses in allokinesis and sunburn-induced itch. We asked whether Merkel cells were important for skin inflammation in the context of cutaneous lupus erythematosus, given the overlap of symptoms. To address this, we bred Merkel cell-deficient mice to our adoptive T-cell transfer cutaneous lupus erythematosus mouse model. Mice lacking half of their Merkel cells had increased skin disease scores compared with littermates and cutaneous lupus erythematosus parental strain controls after adoptive transfer of model autoantigen-specific T cells. Examination of gene expression in the skin revealed increases in CXCL1, IL6, and IL1R2 among other differentially expressed genes. Flow cytometry analysis of skin from Merkel-deficient mice revealed an influx of CD11b+ cells, which was mainly comprised of Ly6G+Ly6C+ neutrophils, compared with genetic controls. We conclude that Merkel cells play a key immunoregulatory role in innate immune system activation in T-cell-driven interface dermatitis.