| Title: |
Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of TH17 cell immunity |
| Authors: |
Lin, Chia-Hao, Wu, Cheng-Jang, Cho, Sunglim, Patkar, Rasika, Huth, William J., Lin, Ling-Li, Chen, Mei-Chi, Israelsson, Elisabeth, Betts, Joanne, Niedzielska, Magdalena, Patel, Shefali A., Duong, Han G., Gerner, Romana R., Hsu, Chia-Yun, Catley, Matthew, Maciewicz, Rose A., Chu, Hiutung, Raffatellu, Manuela, Chang, John T., Lu, Li-Fan |
| Source: |
Nature Immunology; 20230101, Issue: Preprints p1-13, 13p |
| Abstract: |
Regulatory T cells (Tregcells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Tregcells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Tregcells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal Tregcells to regulate helper T17 cell (TH17 cell) immunity. Selectively increased intestinal TH17 cell responses in mice with Tregcell-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+CD62LloTregcell subset that is distinct from previously characterized intestinal Tregcell populations as the main IL-27 producers. Collectively, our study uncovers a new Tregcell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific Tregcell-mediated immune regulation. |
| Database: |
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