Role of MAIT cells in metabolic diseases
Introduction
The prevalence of metabolic diseases has been steadily increasing for more than 30 years in both adults and children (Collaborators et al., 2017). Under physiological conditions, immune cells resident in metabolic tissues help maintain tissue homeostasis (Gebhardt et al., 2018; Klose and Artis, 2016; Mosser et al., 2020). In the development of metabolic diseases, the immune system also plays a central role by favouring chronic inflammation in peripheral tissues, which has been associated with insulin resistance, glucose homeostasis impairment and intestinal microbiota dysbiosis (Dabke et al., 2019; Sell et al., 2012).
MAIT cells, which function at the junction of the innate and adaptive immune system, play an important role against bacterial and viral infections (Kurioka et al., 2015; Le Bourhis et al., 2010; van Wilgenburg et al., 2016). MAIT cells are also involved in tissue repair, in particular in skin and intestine where they participate in the repair in a microbiota-dependent manner (Constantinides et al., 2019; Hinks et al., 2019; Lamichhane et al., 2019; Leng et al., 2019). Several recent studies have also highlighted the role of MAIT cells in metabolic diseases (Carolan et al., 2015; Hegde et al., 2018; Magalhaes et al., 2015; O’Brien et al., 2019; Toubal et al., 2020; Touch et al., 2018; Zhang et al., 2019).
This review focuses on MAIT cells in metabolic diseases, where we describe MAIT cell alterations and then discuss disease mechanisms inducing MAIT cell activation and their involvement in disease pathogenesis.
Section snippets
MAIT cells in obesity and type 2 diabetes
Obesity and type 2 diabetes (T2D) are associated with chronic, low-grade inflammation following a disruption of the immune system, as well as an alteration of the intestinal microbiota. MAIT cells are greatly impacted in these diseases. In humans, the frequency of blood circulating MAIT cells is dramatically reduced in obese and diabetic patients, compared to healthy subjects (Carolan et al., 2015; Magalhaes et al., 2015). MAIT frequency is negatively correlated with body mass index (BMI) and
Role of bacterial and endogenous ligands
MAIT cells is closely linked to the microbiota, which is essential for MAIT cell development and expansion (Legoux et al., 2020; Treiner et al., 2003). Indeed, MAIT cell activator ligands have been identified as soluble microbial derivatives from the vitamin B2 biosynthesis pathway (Corbett et al., 2014; Kjer-Nielsen et al., 2012). After the early studies, which emphasized vitamin B metabolites, newer agonist and inhibitory ligands have been identified (Keller et al., 2017; Salio et al., 2020).
Role of inflammation
In humans and mice, MAIT cells express a wide range of cytokine and chemokine receptors (Bertrand and Lehuen, 2019; Dusseaux et al., 2011; Rahimpour et al., 2015; Toubal et al., 2019; Ussher et al., 2014), which allow their migration to and their activation within inflamed tissue. In the context of bacterial or viral infection, MAIT cells can be activated in a TCR-independent and cytokine-dependent manner via IL-12, IL-15 or IL-18 (Loh et al., 2016; van Wilgenburg et al., 2016), and these
Role of glucose
Impairment of glucose homeostasis is one of the hallmarks of metabolic diseases (Gregor and Hotamisligil, 2011; Ormazabal et al., 2018; Pagano et al., 2002). Despite the importance of glycolysis pathway in T cell activation and effector function (Shyer et al., 2020), only a few studies have explored in the context of metabolic diseases whether MAIT cells undergo a metabolic reprogramming that can impact their phenotype. In obesity and CMDs, blood MAIT cell frequency is negatively correlated to
Conclusion
In recent years MAIT cells have emerged as important effectors in several metabolic diseases (Carolan et al., 2015; Hegde et al., 2018; Magalhaes et al., 2015; O’Brien et al., 2019; Toubal et al., 2020; Touch et al., 2018). In these diseases, chronic inflammation, glucotoxicity as well as dysbiosis are associated with MAIT cell frequency and phenotype alteration. MAIT cells are activated and produce proinflammatory cytokines contributing to chronic inflammation and metabolic dysregulation.
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
A.T. and A.L. are supported by ANR11-IDEX-0005-02 Laboratory of Excellence INFLAMEX; A.T. was also supported by RHU QUID-NASH; A.L. is supported by ANR-14-CE12-0018, ANR-15-CE14-0029-03, ANR-19-CE14-0020, the Société Francophone de Diabète, Fondation Francophone pour la Recherche sur le Diabète, Fondation pour la Recherche Médicale (EQU201903007779) and the European Foundation for the Study of Diabetes to A.L. and A.T. Servier Medical Art for the free medical images (licensed under a Creative
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