GPR15-C10ORF99 functional pairing initiates colonic Treg homing in amniotes.
GPR15-C10ORF99 functional pairing initiates colonic Treg homing in amniotes.
复制标题
DOI：
10.15252/embr.202153246
复制
发表时间：
2022-02-03
期刊：
影响因子：
7.7
通讯作者：
Deng C
中科院分区：
文献类型：
--
作者：
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
由G蛋白偶联受体（GPCR）-配体相互作用介导的调节性T淋巴细胞（Treg）归巢反应通过抑制胃肠道中的不适当免疫应答在维持肠道免疫稳态中发挥核心作用。然而，Treg归巢结肠的起源仍然是个谜。在这里，我们报告了C10 ORF 99肽（也称为CPR 15 L和AP 57），GPR 15的同源配体，控制Treg归巢到结肠，起源于侧翼CDHR 1基因的复制，并在功能上与GPR 15配对。进化分析和实验数据表明，GPR 15-C10 ORF 99对在介导结肠Treg归巢方面是功能保守的，并且它们的表达模式与结肠中的草食动物饮食正相关。随着早期蝾螈的第一次食草饮食，出现了一个新的生物过程（食草饮食短链脂肪酸-C10 ORF 99/GPR 15诱导的Treg归巢结肠免疫稳态），我们提出了一个进化模型，即GPR 15-C10 ORF 99功能配对启动了蝾螈的第一次结肠Treg归巢反应。我们的研究结果还强调，GPCR配体配对导致脊椎动物进化过程中的生理适应。GPR 15-C10 ORF 99对在功能上保守以介导结肠Treg归巢。它们的表达模式与草食动物饮食正相关，表明这种功能配对启动了第一个结肠Treg归巢反应。
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. The GPR15–C10ORF99 pair is functionally conserved to mediate colonic Treg homing in amniotes. Their expression patterns are positively correlated with herbivore diet, suggesting that this functional pairing initiates the first colonic Treg homing reaction in amniotes.
登录
查看更多内容
影响因子：
4.7
作者：
Fournier, David;Luft, Friedrich C.;Bader, Michael;Ganten, Detlev;Andrade-Navarro, Miguel A.
通讯作者：
Andrade-Navarro, Miguel A.
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
64.5
作者：
Foster, Simon R.;Hauser, Alexander S.;Gloriam, David E.
通讯作者：
Gloriam, David E.
影响因子：
4.6
作者：
Bian C;Hu Y;Ravi V;Kuznetsova IS;Shen X;Mu X;Sun Y;You X;Li J;Li X;Qiu Y;Tay BH;Thevasagayam NM;Komissarov AS;Trifonov V;Kabilov M;Tupikin A;Luo J;Liu Y;Song H;Liu C;Wang X;Gu D;Yang Y;Li W;Polgar G;Fan G;Zeng P;Zhang H;Xiong Z;Tang Z;Peng C;Ruan Z;Yu H;Chen J;Fan M;Huang Y;Wang M;Zhao X;Hu G;Yang H;Wang J;Wang J;Xu X;Song L;Xu G;Xu P;Xu J;O'Brien SJ;Orbán L;Venkatesh B;Shi Q
通讯作者：
Shi Q
影响因子：
3.2
作者：
Johnson EL;Singh R;Singh S;Johnson-Holiday CM;Grizzle WE;Partridge EE;Lillard JW Jr
通讯作者：
Lillard JW Jr