| Title: | GPR15-C10ORF99 functional pairing initiates colonic Treg homing in amniotes |
| Author(s): | Song J; Zheng H; Xue J; Liu J; Sun Q; Yang W; Liu F; Xiang X; He K; Chen Y; Cheng J; Li W; Jin J; Brosius J; Deng C; |
| Address: | "Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, China. MOE Laboratory of Biosystem Homeostasis and Protection, and Life Sciences Institute, Zhejiang University, Hangzhou, China" |
| ISSN/ISBN: | 1469-3178 (Electronic) 1469-221X (Print) 1469-221X (Linking) |
| Abstract: | "Regulatory T lymphocyte (Treg) homing reactions mediated by G protein-coupled receptor (GPCR)-ligand interactions play a central role in maintaining intestinal immune homeostasis by restraining inappropriate immune responses in the gastrointestinal tract. However, the origin of Treg homing to the colon remains mysterious. Here, we report that the C10ORF99 peptide (also known as CPR15L and AP57), a cognate ligand of GPR15 that controls Treg homing to the colon, originates from a duplication of the flanking CDHR1 gene and is functionally paired with GPR15 in amniotes. Evolutionary analysis and experimental data indicate that the GPR15-C10ORF99 pair is functionally conserved to mediate colonic Treg homing in amniotes and their expression patterns are positively correlated with herbivore diet in the colon. With the first herbivorous diet in early amniotes, a new biological process (herbivorous diet short-chain fatty acid-C10ORF99/GPR15-induced Treg homing colon immune homeostasis) emerged, and we propose an evolutionary model whereby GPR15-C10ORF99 functional pairing has initiated the first colonic Treg homing reaction in amniotes. Our findings also highlight that GPCR-ligand pairing leads to physiological adaptation during vertebrate evolution" |
| Keywords: | "Animals *Antimicrobial Cationic Peptides Colon/*cytology/immunology *DNA-Binding Proteins Ligands Protein Binding *Receptors, G-Protein-Coupled/genetics/metabolism *T-Lymphocytes, Regulatory/cytology C10orf99 Gpr15 adaptive evolution colonic Treg homing p;" |
| Notes: | "MedlineSong, Jingjing Zheng, Huaping Xue, Jingwen Liu, Jian Sun, Qian Yang, Wei Liu, Fang Xiang, Xiangyin He, Kai Chen, Younan Cheng, Jingqiu Li, Wei Jin, Jin Brosius, Juergen Deng, Cheng eng Research Support, Non-U.S. Gov't England 2021/12/24 EMBO Rep. 2022 Feb 3; 23(3):e53246. doi: 10.15252/embr.202153246. Epub 2021 Dec 23" |
