Local IL-23 is required for proliferation and retention of skin-resident memory TH17 cells

SK Whitley, M Li, SW Kashem, T Hirai, BZ Igyártó… - Science …, 2022 - science.org
SK Whitley, M Li, SW Kashem, T Hirai, BZ Igyártó, K Knizner, J Ho, LK Ferris, CT Weaver…
Science immunology, 2022science.org
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 (TRM) cell–mediated protection from C. albicans
reinfection required IL-23. Administration of anti–IL-23 receptor antibody to mice after …
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 (TRM) 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 (TRM17) cells from skin, and clinical anti–IL-23 therapy depleted TRM17 cells from skin of patients with psoriasis. IL-23 receptor blockade impaired TRM17 cell proliferation but did not affect apoptosis susceptibility or tissue egress. IL-23 produced by CD301b+ myeloid cells was required for TRM17 maintenance in skin after C. albicans infection, and CD301b+ cells were necessary for TRM17 expansion during the development of imiquimod dermatitis. This study demonstrates that locally produced IL-23 promotes in situ proliferation of cutaneous TRM17 cells to support their longevity and function and provides mechanistic insight into the durable efficacy of IL-23 blockade in the treatment of psoriasis.
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