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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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PD-1 deficiency protects experimental colitis via alteration of gut microbiota

  • Park, Seong Jeong (Department of Life Sciences, Pohang University of Science and Technology) ;
  • Kim, Ji-Hae (Department of Life Sciences, Pohang University of Science and Technology) ;
  • Song, Mi-Young (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) ;
  • Sung, Young Chul (Department of Life Sciences, Pohang University of Science and Technology) ;
  • Lee, Seung-Woo (Department of Life Sciences, Pohang University of Science and Technology) ;
  • Park, Yunji (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology)
  • Received : 2017.08.23
  • Accepted : 2017.09.22
  • Published : 2017.11.30
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Abstract

Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 ($PD-1^{-/-}$) did not develop colon inflammation. Interestingly, $PD-1^{-/-}$ mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of $PD-1^{-/-}$ mice to colitis is dependent on their gut microbiota. 16S rRNA gene-pyrosequencing analysis showed that $PD-1^{-/-}$ mice had altered composition of gut microbiota with significant reduction in Rikenellaceae family. These altered colon bacteria of $PD-1^{-/-}$ mice induced less amount of inflammatory mediators from colon epithelial cells, including interleukin (IL)-6, and inflammatory chemokines. Taken together, our study indicates that PD-1 expression is involved in the resistance to experimental colitis through altered bacterial communities of colon.

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