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Bacteroides ovatus-mediated CD27− MAIT cell activation is associated with obesity-related T2D progression

Cellular & Molecular Immunology volume 19, pages 791–804 (2022)Cite this article

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Abstract

Type 2 diabetes (T2D) is highly associated with obesity. However, the factors that drive the transition from excessive weight gain to glucose metabolism disruption are still uncertain and seem to revolve around systemic immune disorder. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial metabolites, have been reported to be altered in obese people and to lead to metabolic dysfunction during obesity. By studying the immunophenotypes of blood MAIT cells from a cross-sectional cohort of obese participants with/without T2D, we found an elevation in CD27-negative (CD27−) MAIT cells producing a high level of IL-17 under T2D obese conditions, which could be positively correlated with impaired glucose metabolism in obese people. We further explored microbial translocation caused by gut barrier dysfunction in obese people as a triggering factor of MAIT cell abnormalities. Specifically, accumulation of the bacterial strain Bacteroides ovatus in the peripheral blood drove IL-17-producing CD27− MAIT cell expansion and could be associated with T2D risk in obese individuals. Overall, these results suggest that an aberrant gut microbiota–immune axis in obese people may drive or exacerbate T2D. Importantly, CD27− MAIT cell subsets and Bacteroides ovatus could represent targets for novel interventional strategies. Our findings extend current knowledge regarding the clinical relevance of body mass index (BMI)-associated variation in circulating MAIT cells to reveal the role of these cells in obesity-related T2D progression and the underlying cellular mechanisms.

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Acknowledgements

This study was funded by the National Key R&D Program of China (2017YFA0105803), the National Natural Science Foundation of China (32000621 and 81770826), the Key Area R&D Program of Guangdong Province (2019B020227003), the Science and Technology Plan Project of Guangzhou City (202102010338 and 202007040003), the 5010 Clinical Research Projects of Sun Yat-sen University (2015015) and the Dengfeng Plan High-level Hospital Construction Opening Project of Foshan Fourth People’s Hospital (FSSYKF-2020009).

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  1. These authors contributed equally: Yue Li, Yi Yang, Jin Wang, Peihong Cai.

Authors and Affiliations

  1. Department of Endocrinology & Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Yue Li, Yi Yang, Jin Wang, Mei Li, Xixiang Tang, Ying Tan, Yuchan Wang, Fan Zhang, Yuanpeng Nie, Xuemin He, Yanhua Zhu, Guojun Shi & Yanming Chen

  2. Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Peihong Cai & Yan Lu

  3. VIP Medical Service Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Mei Li & Xixiang Tang

  4. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China

    Xiaofeng Wen, Qiaoxing Liang & Lai Wei

  5. Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Tufeng Chen

  6. Department of Rheumatology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, China

    Xiang Peng

  7. Division of Pediatric Nephrology, Rady Children’s Hospital, University of California, San Diego, CA, 92093−0831, USA

    Wai W. Cheung

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Contributions

YL, YY, JW, PC, LW, YC, and YL designed the research; YL, YY, JW, PC, ML, XT, YT, YW, FZ, XW, QL, YN, and YL performed the research; XW, QL, TC, XP, XH, YZ, GS, and WWC contributed new concepts/reagents/research materials/analytical tools; YL, YY, JW, PC, LW, YC, and YL analyzed the data; YL, YY, JW, WWC, LW, YC, and YL wrote the manuscript.

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Correspondence to Lai Wei, Yanming Chen or Yan Lu.

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Li, Y., Yang, Y., Wang, J. et al. Bacteroides ovatus-mediated CD27− MAIT cell activation is associated with obesity-related T2D progression. Cell Mol Immunol 19, 791–804 (2022). https://doi.org/10.1038/s41423-022-00871-4

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