Local IL-23 is required for proliferation and retention of skin-resident memory T <sub>H</sub> 17 cells
Sarah K. Whitley, Mushi Li, Sakeen W. Kashem, Toshiro Hirai, Botond Z. Igyártó, Kelley Knizner, Jonhan Ho, Laura K. Ferris, Casey T. Weaver, Daniel J. Cua, Mandy J. McGeachy, Daniel H. Kaplan
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 Candida albicans skin infection, and tissue-resident memory (T RM ) cell–mediated protection from C. albicans reinfection required IL-23. Administration of anti–IL-23 receptor antibody to mice after resolution of primary C. albicans 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 C. albicans 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.