Tissue adaptation

Science https://doi.org/10.1126/science.aat6280 (2018)

Commensals and commensal-reactive lymphocytes coexist at barrier tissues. In Science, Belkaid and colleagues show that skin-resident commensal-specific T cells express a type 17 program associated with a poised type 2 program. Staphylococcus epidermis–colonized mice develop long-lived, tissue-resident, S. epidermis–specific CD8⁺ memory T cells. S. epidermis–elicited RORγt⁺CD4⁺ T_H17 cells and RORγt⁺CD8⁺ Tc17 cells produce the type 2 cytokines IL-5 and IL-13 after intradermal injection of chitin, sand fly bites or skin-specific deletion of regulatory T cells. During homeostasis, S. epidermis–specific Tc17 cells co-express the transcription factors RORγt and GATA-3 and express a broad GATA-3-dependent type 2 transcriptome (Il5, Il13 and Ccr8, but not Il10 or Il4), without protein translation. Exposure to IL-18 in the context of TCR stimulation triggers production of IL-5 and IL-13 in S. epidermis–specific Tc17 cells and T_H17 cells, regardless of whether they expressed IL-17A previously or not. These results highlight the plasticity and adaptability of tissue-resident commensal-specific T cells.