Immunology of Diabetes

Our research focuses on the role of adaptive and innate immune cells in type 1 (T1D) and type 2 (T2D) diabetes/obesity and genetics of diabetes to understand disease mechanisms, discover biomarkers and develop therapeutic strategies.

PI: Agnès LEHUEN

Image showing cells in an infiltrated pancreatic ilet.

Labeled in red: CD3, T cells ; in green: Glucagon, alpha cells ; in blue: DAPI, cell nuclei

The specific objectives are:
– Determine the role of innate T lymphocytes in the regulation of T1D. NKT and MAIT cells are unconventional T cells that act as sensors of metabolic abnormalities. These innate-like T cells can regulate both innate and adaptive immunity. Our data demonstrated the efficiency of NKT and MAIT cells in preventing T1D.
– Determine the role of innate T lymphocytes in the regulation of T2D, obesity and non-alcoholic fatty liver disease. We have shown that in patients and mouse models, T2D and obesity induce alterations in MAIT cells, and high levels of inflammatory cytokines in adipose tissue. With our collaborators, we have shown that MAIT cells are profibrogenic in the liver of cirrhotic patients associated with non-alcoholic steatohepatitis (NASH).

– Develop “humanized” murine models that more closely mimic human T1D and understand the role of co-stimulation pathways in autoimmune activation against a given self-tissue. Such models are crucial for the initiation of clinical trials exploring vaccination strategies with cell antigens aimed at restoring immune tolerance.
– Identify genetic factors involved in the diversity of juvenile-onset diabetes, ranging from multifactorial T1D to monogenic forms of diabetes whose clinical presentation may be atypical or not.

Team member

A new article from Cécile Haumaitre and collaborators discusses the origin of pancreatic lesions associated with pancreatic cancer

Diabetes Institute, From inflammation to cancer in digestive diseases, Publications

Pancreatic ductal adenocarcinoma is currently the fourth leading cause of cancer death worldwide. It is projected to become the second leading cause of cancer death by 2030. Unfortunately, PDAC is often diagnosed at an advanced stage, resulting in a 5-year survival rate of less than 10%. Since the most common precancerous lesions of PDAC are currently not clinically detectable, understanding the mechanisms that lead to their formation and progression is crucial to enabling early diagnosis and more effective therapeutic intervention.