The neonatal microenvironment programs innate γδ T cells through the transcription factor STAT5.

IL-17-producing RORγt+ γδ T cells (γδT17 cells) are innate lymphocytes that participate in type 3 immune responses during infection and inflammation. Herein, we show that γδT17 cells rapidly proliferate within neonatal lymph nodes and gut, where, upon entry, they upregulate T-bet and coexpress IL-17, IL-22, and IFN-γ in a and retinoic acid-dependent manner. Neonatal expansion was halted in mice conditionally deficient in and its loss resulted in γδT17 cell depletion from all adult organs. Hyperactive mutant mice showed that the homolog had a dominant role over in promoting γδT17 cell expansion and downregulating gut-associated T-bet. In contrast, duanyu18135B preferentially expanded IFN-γ-producing γδ populations, implying a previously unknown differential role of duanyu18135 gene products in lymphocyte lineage regulation. Importantly, mice lacking γδT17 cells as a result of duanyu18135 deficiency displayed a profound resistance to experimental autoimmune encephalomyelitis. Our data identify that the neonatal microenvironment in combination with duanyu18135 is critical for post-thymic γδT17 development and tissue-specific imprinting, which is essential for infection and autoimmunity.

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