Local IL-23 is required for proliferation and retention of skin-resident memory T _H 17 cells

Abstract

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 <i>Candida albicans</i> skin infection, and tissue-resident memory (T_RM) cell-mediated protection from <i>C. albicans</i> reinfection required IL-23. Administration of anti-IL-23 receptor antibody to mice after resolution of primary <i>C. albicans</i> infection resulted in loss of CD69⁺ CD103⁺ tissue-resident memory T helper 17 (T_RM17) cells from skin, and clinical anti-IL-23 therapy depleted T_RM17 cells from skin of patients with psoriasis. IL-23 receptor blockade impaired T_RM17 cell proliferation but did not affect apoptosis susceptibility or tissue egress. IL-23 produced by CD301b⁺ myeloid cells was required for T_RM17 maintenance in skin after <i>C. albicans</i> infection, and CD301b⁺ cells were necessary for T_RM17 expansion during the development of imiquimod dermatitis. This study demonstrates that locally produced IL-23 promotes in situ proliferation of cutaneous T_RM17 cells to support their longevity and function and provides mechanistic insight into the durable efficacy of IL-23 blockade in the treatment of psoriasis.