MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT.
MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT.
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MAIT和Vδ2非常规T细胞受到多种肠道微生物群的支持，并与异体HCT后良好的患者预后相关。
DOI：
10.1126/scitranslmed.abj2829
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发表时间：
2022-05-25
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
--
作者：
微生物多样性与同种异体造血细胞移植（allo-HCT）受者的预后改善相关，但这一观察结果背后的机制尚不清楚。在接受 allo-HCT 的 174 名患者的队列中，我们证明，allo-HCT 后早期肠道微生物群的多样性与先天样粘膜相关不变 T (MAIT) 细胞数量的增加有关，这反过来又与总生存率的提高和移植物抗宿主病 (aGVHD) 的急性程度降低有关。常规和非常规免疫细胞亚群的免疫分析显示，Vδ2 细胞（γδ T 细胞的主要循环亚群）的流行率与 MAIT 细胞的频率密切相关，并且与较少的 aGVHD 相关。使用单细胞转录组学和流式细胞术对这些群体进行分析表明，移植后出现了向激活表型的转变以及细胞毒性和效应功能的获得。具有为 MAIT 和 Vδ2 细胞产生激活配体的能力的多样化肠道微生物组似乎对于异基因 HCT 后维持这些群体是必要的。这些数据表明肠道微生物多样性、微生物衍生配体和非常规 T 细胞的维持之间存在免疫学联系。同种异体 HCT 后，MAIT 和 Vδ2 细胞得到多种肠道微生物组的支持，并与良好的结果相关。
Microbial diversity is associated with improved outcomes in recipients of allogeneic hematopoietic cell transplantation (allo-HCT), but the mechanism underlying this observation is unclear. In a cohort of 174 patients who underwent allo-HCT, we demonstrate that a diverse intestinal microbiome early after allo-HCT is associated with an increased number of innate-like mucosal-associated invariant T (MAIT) cells, which are in turn associated with improved overall survival and less acute graft-versus-host disease (aGVHD). Immune profiling of conventional and unconventional immune cell subsets revealed that the prevalence of Vδ2 cells, the major circulating subpopulation of γδ T cells, closely correlated with the frequency of MAIT cells and was associated with less aGVHD. Analysis of these populations using both single cell transcriptomics and flow cytometry suggested a shift toward activated phenotypes and a gain of cytotoxic and effector functions after transplantation. A diverse intestinal microbiome with the capacity to produce activating ligands for MAIT and Vδ2 cells appeared to be necessary for the maintenance of these populations after allo-HCT. These data suggest an immunological link between intestinal microbial diversity, microbe-derived ligands, and maintenance of unconventional T cells. MAIT and Vδ2 cells are supported by a diverse intestinal microbiome after allogeneic HCT and correlate with favorable outcome.
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影响因子：
14.9
作者：
Howe KL;Achuthan P;Allen J;Allen J;Alvarez-Jarreta J;Amode MR;Armean IM;Azov AG;Bennett R;Bhai J;Billis K;Boddu S;Charkhchi M;Cummins C;Da Rin Fioretto L;Davidson C;Dodiya K;El Houdaigui B;Fatima R;Gall A;Garcia Giron C;Grego T;Guijarro-Clarke C;Haggerty L;Hemrom A;Hourlier T;Izuogu OG;Juettemann T;Kaikala V;Kay M;Lavidas I;Le T;Lemos D;Gonzalez Martinez J;Marugán JC;Maurel T;McMahon AC;Mohanan S;Moore B;Muffato M;Oheh DN;Paraschas D;Parker A;Parton A;Prosovetskaia I;Sakthivel MP;Salam AIA;Schmitt BM;Schuilenburg H;Sheppard D;Steed E;Szpak M;Szuba M;Taylor K;Thormann A;Threadgold G;Walts B;Winterbottom A;Chakiachvili M;Chaubal A;De Silva N;Flint B;Frankish A;Hunt SE;IIsley GR;Langridge N;Loveland JE;Martin FJ;Mudge JM;Morales J;Perry E;Ruffier M;Tate J;Thybert D;Trevanion SJ;Cunningham F;Yates AD;Zerbino DR;Flicek P
通讯作者：
Flicek P
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
DOI：
10.1084/jem.20171739
发表时间：
2018-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ben Youssef G;Tourret M;Salou M;Ghazarian L;Houdouin V;Mondot S;Mburu Y;Lambert M;Azarnoush S;Diana JS;Virlouvet AL;Peuchmaur M;Schmitz T;Dalle JH;Lantz O;Biran V;Caillat-Zucman S
通讯作者：
Caillat-Zucman S
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
DOI：
10.1126/science.aax6624
发表时间：
2019-10-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y
通讯作者：
Belkaid Y