1. MAIT cells in T2D diabetes, obesity and nonalcoholic liver steatosis. Converging data highlight the role of innate-like T cells, such as NKT and MAIT (Mucosal Associated Invariant T) cells, which represent a first line of T responder lymphocytes controlling the fate of immune responses. The potential role of the gut microbiota in metabolic and liver diseases led us to investigate the MAIT cells that recognized bacterial ligands and are preferably located in the intestinal mucosa and the liver. We are investigating the potential link between MAIT cells, inflammation and dysbiosis in obesity and liver disease using human samples and animal models. Our goal is to determine whether MAIT cell alterations are causal with the goal of developing innovative strategies based on MAIT cell manipulation.

2. Genetic pathways in T2D diabetes, obesity and nonalcoholic liver steatosis. We are developing new models to study the involved genetic pathways in disease development. A particular focus is give on genes that are likely to regulate the circadian coordination of the immune system and metabolism.

1. In T2D and obese patients circulating MAIT cells are altered and produce high levels of inflammatory cytokines (e.g. IL-17) in the adipose tissue. We have developed mouse models expressing various frequencies of MAIT cells and we are analysing the impact of MAIT cells on insulin resistance and glucose intolerance, associated with increased inflammation in adipose tissue and the intestine. In parallel we continue studies in T2D and obese patients.
2. We have developed mouse models that are invalidated for the circadian gene Arntl2 (Bmal2) and address the question if the resulting increase in immune activation contributes to diabetes and obesity.

We are grateful to have received recent funding from the AFEF and SFD/ Roche awarded to Amine Toubal.

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