Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesity

Abstract Introduction Gut microbiota has been reported to contribute to obesity and the pathology of obesity‐related diseases but the underlying mechanisms are largely unknown. Mucosal‐associated invariant T (MAIT) cells are a unique subpopulation of T cells characterized by the expression of a semi...

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Main Authors: Jianyun Liu, Hongmei Nan, Randy R Brutkiewicz, Jose Casasnovas, Kok Lim Kua
Format: Article
Language:English
Published: Wiley 2021-03-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.393
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author Jianyun Liu
Hongmei Nan
Randy R Brutkiewicz
Jose Casasnovas
Kok Lim Kua
author_facet Jianyun Liu
Hongmei Nan
Randy R Brutkiewicz
Jose Casasnovas
Kok Lim Kua
author_sort Jianyun Liu
collection DOAJ
description Abstract Introduction Gut microbiota has been reported to contribute to obesity and the pathology of obesity‐related diseases but the underlying mechanisms are largely unknown. Mucosal‐associated invariant T (MAIT) cells are a unique subpopulation of T cells characterized by the expression of a semi‐invariant T cell receptor (TCR) α chain (Vα19 in mice; Vα7.2 in humans). The expansion and maturation of MAIT cells require the gut microbiota and antigen‐presenting molecule MR1, suggesting that MAIT cells may play a unique role in bridging gut microbiota, obesity, and obesity‐associated inflammation. Methods The levels of human MAIT cells from obese patients, as well as mouse MAIT cells from obese mouse models, were determined by flow cytometry. By comparing to controls, we analyzed the change of MAIT cells in obese subjects. Results We found obese patients had fewer circulating MAIT cells than healthy‐weight donors and the difference was more distinct in male patients. Consistently, male mice (but not female mice) have shown reduced MAIT cells in the liver and adipose tissue after a 10‐week Western diet compared to mice on a control diet. We also explored the possibility of utilizing high‐throughput technology (i.e., quantitative polymerase chain reaction [qPCR]), other than flow cytometry, to determine the expression levels of the invariant TCR of human MAIT cells. But a minimal correlation (R2 = 0.23, p = .11) was observed between qPCR and flow cytometry data. Conclusion Our study suggests that there is a sex discrepancy in the impact of obesity on MAIT cells: MAIT cells in male (but not female) humans and male mice are reduced by obesity.
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spelling doaj-art-623c20cc2e1840bba5f30895830352c32025-08-20T03:06:15ZengWileyImmunity, Inflammation and Disease2050-45272021-03-019129930910.1002/iid3.393Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesityJianyun Liu0Hongmei Nan1Randy R Brutkiewicz2Jose Casasnovas3Kok Lim Kua4Department of Microbiology and Immunology Indiana University School of Medicine Indianapolis Indiana USADepartment of Global Health, Richard M. Fairbanks School of Public Health Indiana University Indianapolis Indiana USADepartment of Microbiology and Immunology Indiana University School of Medicine Indianapolis Indiana USADepartment of Pediatrics Indiana University School of Medicine Indianapolis Indiana USADepartment of Pediatrics Indiana University School of Medicine Indianapolis Indiana USAAbstract Introduction Gut microbiota has been reported to contribute to obesity and the pathology of obesity‐related diseases but the underlying mechanisms are largely unknown. Mucosal‐associated invariant T (MAIT) cells are a unique subpopulation of T cells characterized by the expression of a semi‐invariant T cell receptor (TCR) α chain (Vα19 in mice; Vα7.2 in humans). The expansion and maturation of MAIT cells require the gut microbiota and antigen‐presenting molecule MR1, suggesting that MAIT cells may play a unique role in bridging gut microbiota, obesity, and obesity‐associated inflammation. Methods The levels of human MAIT cells from obese patients, as well as mouse MAIT cells from obese mouse models, were determined by flow cytometry. By comparing to controls, we analyzed the change of MAIT cells in obese subjects. Results We found obese patients had fewer circulating MAIT cells than healthy‐weight donors and the difference was more distinct in male patients. Consistently, male mice (but not female mice) have shown reduced MAIT cells in the liver and adipose tissue after a 10‐week Western diet compared to mice on a control diet. We also explored the possibility of utilizing high‐throughput technology (i.e., quantitative polymerase chain reaction [qPCR]), other than flow cytometry, to determine the expression levels of the invariant TCR of human MAIT cells. But a minimal correlation (R2 = 0.23, p = .11) was observed between qPCR and flow cytometry data. Conclusion Our study suggests that there is a sex discrepancy in the impact of obesity on MAIT cells: MAIT cells in male (but not female) humans and male mice are reduced by obesity.https://doi.org/10.1002/iid3.393MAITobesitysex discrepancy
spellingShingle Jianyun Liu
Hongmei Nan
Randy R Brutkiewicz
Jose Casasnovas
Kok Lim Kua
Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesity
Immunity, Inflammation and Disease
MAIT
obesity
sex discrepancy
title Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesity
title_full Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesity
title_fullStr Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesity
title_full_unstemmed Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesity
title_short Sex discrepancy in the reduction of mucosal‐associated invariant T cells caused by obesity
title_sort sex discrepancy in the reduction of mucosal associated invariant t cells caused by obesity
topic MAIT
obesity
sex discrepancy
url https://doi.org/10.1002/iid3.393
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AT hongmeinan sexdiscrepancyinthereductionofmucosalassociatedinvarianttcellscausedbyobesity
AT randyrbrutkiewicz sexdiscrepancyinthereductionofmucosalassociatedinvarianttcellscausedbyobesity
AT josecasasnovas sexdiscrepancyinthereductionofmucosalassociatedinvarianttcellscausedbyobesity
AT koklimkua sexdiscrepancyinthereductionofmucosalassociatedinvarianttcellscausedbyobesity