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The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation

Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activa...

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Autores principales: Gao, Meng-Ge, Hong, Yan, Zhao, Xiang-Yu, Pan, Xin-An, Sun, Yu-Qian, Kong, Jun, Wang, Zhi-Dong, Wang, Feng-Rong, Wang, Jing-Zhi, Yan, Chen-Hua, Wang, Yu, Huang, Xiao-Jun, Zhao, Xiao-Su
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448388/
https://www.ncbi.nlm.nih.gov/pubmed/34539656
http://dx.doi.org/10.3389/fimmu.2021.720354
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author Gao, Meng-Ge
Hong, Yan
Zhao, Xiang-Yu
Pan, Xin-An
Sun, Yu-Qian
Kong, Jun
Wang, Zhi-Dong
Wang, Feng-Rong
Wang, Jing-Zhi
Yan, Chen-Hua
Wang, Yu
Huang, Xiao-Jun
Zhao, Xiao-Su
author_facet Gao, Meng-Ge
Hong, Yan
Zhao, Xiang-Yu
Pan, Xin-An
Sun, Yu-Qian
Kong, Jun
Wang, Zhi-Dong
Wang, Feng-Rong
Wang, Jing-Zhi
Yan, Chen-Hua
Wang, Yu
Huang, Xiao-Jun
Zhao, Xiao-Su
author_sort Gao, Meng-Ge
collection PubMed
description Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation [non-T-cell receptor (TCR) signal] and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells in vitro. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans.
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spelling pubmed-84483882021-09-18 The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation Gao, Meng-Ge Hong, Yan Zhao, Xiang-Yu Pan, Xin-An Sun, Yu-Qian Kong, Jun Wang, Zhi-Dong Wang, Feng-Rong Wang, Jing-Zhi Yan, Chen-Hua Wang, Yu Huang, Xiao-Jun Zhao, Xiao-Su Front Immunol Immunology Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation [non-T-cell receptor (TCR) signal] and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells in vitro. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans. Frontiers Media S.A. 2021-09-03 /pmc/articles/PMC8448388/ /pubmed/34539656 http://dx.doi.org/10.3389/fimmu.2021.720354 Text en Copyright © 2021 Gao, Hong, Zhao, Pan, Sun, Kong, Wang, Wang, Wang, Yan, Wang, Huang and Zhao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Gao, Meng-Ge
Hong, Yan
Zhao, Xiang-Yu
Pan, Xin-An
Sun, Yu-Qian
Kong, Jun
Wang, Zhi-Dong
Wang, Feng-Rong
Wang, Jing-Zhi
Yan, Chen-Hua
Wang, Yu
Huang, Xiao-Jun
Zhao, Xiao-Su
The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
title The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
title_full The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
title_fullStr The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
title_full_unstemmed The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
title_short The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
title_sort potential roles of mucosa-associated invariant t cells in the pathogenesis of gut graft-versus-host disease after hematopoietic stem cell transplantation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448388/
https://www.ncbi.nlm.nih.gov/pubmed/34539656
http://dx.doi.org/10.3389/fimmu.2021.720354
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