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Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of TH17 cell immunity

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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.
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  Data: Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of TH17 cell immunity
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  Data: <searchLink fieldCode="AR" term="%22Lin%2C+Chia-Hao%22">Lin, Chia-Hao</searchLink><br /><searchLink fieldCode="AR" term="%22Wu%2C+Cheng-Jang%22">Wu, Cheng-Jang</searchLink><br /><searchLink fieldCode="AR" term="%22Cho%2C+Sunglim%22">Cho, Sunglim</searchLink><br /><searchLink fieldCode="AR" term="%22Patkar%2C+Rasika%22">Patkar, Rasika</searchLink><br /><searchLink fieldCode="AR" term="%22Huth%2C+William+J%2E%22">Huth, William J.</searchLink><br /><searchLink fieldCode="AR" term="%22Lin%2C+Ling-Li%22">Lin, Ling-Li</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Mei-Chi%22">Chen, Mei-Chi</searchLink><br /><searchLink fieldCode="AR" term="%22Israelsson%2C+Elisabeth%22">Israelsson, Elisabeth</searchLink><br /><searchLink fieldCode="AR" term="%22Betts%2C+Joanne%22">Betts, Joanne</searchLink><br /><searchLink fieldCode="AR" term="%22Niedzielska%2C+Magdalena%22">Niedzielska, Magdalena</searchLink><br /><searchLink fieldCode="AR" term="%22Patel%2C+Shefali+A%2E%22">Patel, Shefali A.</searchLink><br /><searchLink fieldCode="AR" term="%22Duong%2C+Han+G%2E%22">Duong, Han G.</searchLink><br /><searchLink fieldCode="AR" term="%22Gerner%2C+Romana+R%2E%22">Gerner, Romana R.</searchLink><br /><searchLink fieldCode="AR" term="%22Hsu%2C+Chia-Yun%22">Hsu, Chia-Yun</searchLink><br /><searchLink fieldCode="AR" term="%22Catley%2C+Matthew%22">Catley, Matthew</searchLink><br /><searchLink fieldCode="AR" term="%22Maciewicz%2C+Rose+A%2E%22">Maciewicz, Rose A.</searchLink><br /><searchLink fieldCode="AR" term="%22Chu%2C+Hiutung%22">Chu, Hiutung</searchLink><br /><searchLink fieldCode="AR" term="%22Raffatellu%2C+Manuela%22">Raffatellu, Manuela</searchLink><br /><searchLink fieldCode="AR" term="%22Chang%2C+John+T%2E%22">Chang, John T.</searchLink><br /><searchLink fieldCode="AR" term="%22Lu%2C+Li-Fan%22">Lu, Li-Fan</searchLink>
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  Data: Nature Immunology; 20230101, Issue: Preprints p1-13, 13p
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.
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        Value: 10.1038/s41590-023-01667-y
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        Text: English
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              Text: 20230101
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