Mucosal-associated invariant T cells improve nonalcoholic fatty liver disease through regulating macrophage Polarization

Yanmei Li, Bingyuan Huang, Xiang Jiang, Weihua Chen, Jun Zhang, Yiran Wei, Yong Chen, Min Lian, Zhaolian Bian, Qi Miao, Yanshen Peng, Jingyuan Fang, Qixia Wang, Ruqi Tang, M. Eric Gershwin, Xiong Ma

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride. Functional alterations of circulating MAIT cells were also detected in NAFLD patients, such as the increased production of IL-4 whereas the decreased production of IFN-γ and TNF-α. Furthermore, elevated expression of CXCR6 was observed in circulating MAIT cells of patients. Meanwhile, we found an increased number of MAIT cells in the livers of NAFLD, and the number was even greater in patients with higher NAFLD activity score. Moreover, activated MAIT cells induced monocytes/macrophages differentiation into M2 phenotype in vitro. Additionally, MAIT cells were enriched and displayed Th2 type cytokines profile in livers of wild type mice fed with methionine and choline deficient diet (MCD). Notably, mice deficient of MAIT cells exhibited more severe hepatic steatosis and inflammation upon MCD, accompanied with more CD11c+ proinflammatory macrophages (M1) and less CD206+ anti-inflammatory macrophages (M2) in livers. Our results indicate that MAIT cells protect against inflammation in NAFLD through producing regulatory cytokines and inducing anti-inflammatory macrophage polarization, which may provide novel therapeutic strategies for NAFLD.

Original languageEnglish (US)
Article number1994
JournalFrontiers in Immunology
Volume9
Issue numberSEP
DOIs
StatePublished - Sep 4 2018

Fingerprint

Macrophages
Liver
Choline
Methionine
Anti-Inflammatory Agents
Mucosal-Associated Invariant T Cells
Non-alcoholic Fatty Liver Disease
Cytokines
Diet
Inflammation
Phenotype
Transferases
Interleukin-4
Autoimmune Diseases
Monocytes
Triglycerides
Lymphocytes
Serum
Population

Keywords

  • Cytokine
  • Macrophage
  • MR1
  • Mucosal-associated invariant T cell
  • Nonalcoholic fatty liver disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mucosal-associated invariant T cells improve nonalcoholic fatty liver disease through regulating macrophage Polarization. / Li, Yanmei; Huang, Bingyuan; Jiang, Xiang; Chen, Weihua; Zhang, Jun; Wei, Yiran; Chen, Yong; Lian, Min; Bian, Zhaolian; Miao, Qi; Peng, Yanshen; Fang, Jingyuan; Wang, Qixia; Tang, Ruqi; Gershwin, M. Eric; Ma, Xiong.

In: Frontiers in Immunology, Vol. 9, No. SEP, 1994, 04.09.2018.

Research output: Contribution to journalArticle

Li, Y, Huang, B, Jiang, X, Chen, W, Zhang, J, Wei, Y, Chen, Y, Lian, M, Bian, Z, Miao, Q, Peng, Y, Fang, J, Wang, Q, Tang, R, Gershwin, ME & Ma, X 2018, 'Mucosal-associated invariant T cells improve nonalcoholic fatty liver disease through regulating macrophage Polarization', Frontiers in Immunology, vol. 9, no. SEP, 1994. https://doi.org/10.3389/fimmu.2018.01994
Li, Yanmei ; Huang, Bingyuan ; Jiang, Xiang ; Chen, Weihua ; Zhang, Jun ; Wei, Yiran ; Chen, Yong ; Lian, Min ; Bian, Zhaolian ; Miao, Qi ; Peng, Yanshen ; Fang, Jingyuan ; Wang, Qixia ; Tang, Ruqi ; Gershwin, M. Eric ; Ma, Xiong. / Mucosal-associated invariant T cells improve nonalcoholic fatty liver disease through regulating macrophage Polarization. In: Frontiers in Immunology. 2018 ; Vol. 9, No. SEP.
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abstract = "Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride. Functional alterations of circulating MAIT cells were also detected in NAFLD patients, such as the increased production of IL-4 whereas the decreased production of IFN-γ and TNF-α. Furthermore, elevated expression of CXCR6 was observed in circulating MAIT cells of patients. Meanwhile, we found an increased number of MAIT cells in the livers of NAFLD, and the number was even greater in patients with higher NAFLD activity score. Moreover, activated MAIT cells induced monocytes/macrophages differentiation into M2 phenotype in vitro. Additionally, MAIT cells were enriched and displayed Th2 type cytokines profile in livers of wild type mice fed with methionine and choline deficient diet (MCD). Notably, mice deficient of MAIT cells exhibited more severe hepatic steatosis and inflammation upon MCD, accompanied with more CD11c+ proinflammatory macrophages (M1) and less CD206+ anti-inflammatory macrophages (M2) in livers. Our results indicate that MAIT cells protect against inflammation in NAFLD through producing regulatory cytokines and inducing anti-inflammatory macrophage polarization, which may provide novel therapeutic strategies for NAFLD.",
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