Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity

Lin, C.-H.; Wu, C.-J.; Cho, S.; Patkar, R.; Lin, L.-L.; Chen, M.-C.; Israelsson, E.; Betts, J.; Niedzielska, M.; Patel, S. A.; Duong, H. G.; Gerner, R. R.; Hsu, C.-Y.; Catley, M.; Maciewicz, R. A.; Chu, H.; Raffatellu, M.; Chang, J. T.; Lu, L.-F.

doi:10.1101/2023.02.20.529261

bioRxiv · 10.1101/2023.02.20.529261

Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity

Lin, C.-H.·Wu, C.-J.·Cho, S.·Patkar, R.·Lin, L.-L.·Chen, M.-C.·Israelsson, E.·Betts, J.·Niedzielska, M.·Patel, S. A.·Duong, H. G.·Gerner, R. R.·Hsu, C.-Y.·Catley, M.·Maciewicz, R. A.·Chu, H.·Raffatellu, M.·Chang, J. T.·Lu, L.-F.

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Abstract

Regulatory T (Treg) cells are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, here we show that IL-27 is specifically produced by intestinal Treg cells to regulate Th17 immunity. Selectively increased intestinal Th17 responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+TCF1+ Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a novel Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue, and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.

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Lin, C.-H., Wu, C.-J., Cho, S., Patkar, R., Lin, L.-L., Chen, M.-C., Israelsson, E., Betts, J., Niedzielska, M., Patel, S. A., Duong, H. G., Gerner, R. R., Hsu, C.-Y., Catley, M., Maciewicz, R. A., Chu, H., Raffatellu, M., Chang, J. T., Lu, L.-F.. 2023-02-21. Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity. https://doi.org/10.1101/2023.02.20.529261

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