Reconstitution of Circulating Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation: Its Association with the Riboflavin Synthetic Pathway of Gut Microbiota in Cord Blood Transplant Recipients

Reconstitution of Circulating Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation: Its Association with the Riboflavin Synthetic Pathway of Gut Microbiota in Cord Blood Transplant Recipients
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DOI:
10.4049/jimmunol.1900681
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发表时间:
2020-03-15
影响因子:
4.4
通讯作者:
Tojo, Arinobu
Tojo, Arinobu
中科院分区:
医学2区
文献类型:
--
作者:
Konuma, Takaaki;Kohara, Chisato;Tojo, Arinobu

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粘膜相关不变T(MAIT)细胞是一种类型的先天淋巴细胞,并识别由MHC相关蛋白1呈递的核黄素(维生素B2)合成产物。我们研究了173例成人异基因造血细胞移植后MAIT细胞的长期重建及其与慢性移植物抗宿主病(cGVHD)的关系。根据供体来源,MAIT细胞数量与脐带血移植(CBT)后的时间显著相关,但与骨髓移植或外周血干细胞移植后的时间无关。与无cGVHD的患者相比,cGVHD患者的MAIT细胞数量显著降低。我们还检查了MAIT细胞重建和肠道微生物群之间的关联,通过对27名接受CBT的成年患者在CBT后1个月的粪便样本进行16S核糖体测序进行评估。肠道菌群的多样性与CBT后更好的MAIT细胞重建呈正相关。通过重建未观察状态分析进行的群落系统发育调查表明,在CBT后随后进行MAIT细胞重建的患者的微生物组中,ribB和ribA基因的量显著较高。总之,长期MAIT细胞重建取决于供体来源的类型。我们的数据还揭示了循环MAIT细胞与人类肠道微生物群相互作用的重要作用。
Mucosal-associated invariant T (MAIT) cells are a type of innate lymphocyte and recognize riboflavin (vitamin B2) synthesis products presented by MHC-related protein 1. We investigated long-term reconstitution of MAIT cells and its association with chronic graft-versus-host disease (cGVHD) in a cross-sectional cohort of 173 adult patients after allogeneic hematopoietic cell transplantation. According to donor source, the number of MAIT cells significantly correlated with time after cord blood transplantation (CBT) but not with time after bone marrow transplantation or peripheral blood stem cell transplantation. The number of MAIT cells was significantly lower in patients with cGVHD compared with patients without cGVHD. We also examined the association between MAIT cell reconstitution and gut microbiota as evaluated by 16S ribosomal sequencing of stool samples 1 mo post-CBT in 27 adult patients undergoing CBT. The diversity of gut microbiota was positively correlated with better MAIT cell reconstitution after CBT. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis indicated that amounts of ribB and ribA genes were significantly higher in the microbiomes of patients with subsequent MAIT cell reconstitution after CBT. In conclusion, long-term MAIT cell reconstitution is dependent on the type of donor source. Our data also unveiled an important role for the interaction of circulating MAIT cells with gut microbiota in humans.