Local IL-23 is required for proliferation and retention of skin-resident memory T17 cells.

The cytokine interleukin-23 (IL-23) is critical for development and maintenance of autoimmune inflammation in nonlymphoid tissues; however, the mechanism through which IL-23 supports tissue-specific immunity remains unclear. In mice, we found that circulating memory T cells were dispensable for anamnestic protection from skin infection, and tissue-resident memory (T) cell-mediated protection from reinfection required IL-23. Administration of anti-IL-23 receptor antibody to mice after resolution of primary infection resulted in loss of CD69 CD103 tissue-resident memory T helper 17 (T) cells from skin, and clinical anti-IL-23 therapy depleted T cells from skin of patients with psoriasis. IL-23 receptor blockade impaired T cell proliferation but did not affect apoptosis susceptibility or tissue egress. IL-23 produced by CD301b myeloid cells was required for T maintenance in skin after infection, and CD301b cells were necessary for T expansion during the development of imiquimod dermatitis. This study demonstrates that locally produced IL-23 promotes in situ proliferation of cutaneous T cells to support their longevity and function and provides mechanistic insight into the durable efficacy of IL-23 blockade in the treatment of psoriasis.