Innate and adaptive immune pathways in autoimmunity and auto-inflammation

We are interested in cell biological and metabolic control of TLR activation and MHC class I cross-presentation

We focus on regulation of beta cell-directed autoimmunity by antimicrobial peptides and the intrinsic beta cell reponse

Members of the team

from left to right: Julien Diana, Maeva Agapoff, Emmanuelle Waeckel-Énée, Nadia Keelan, Barbara Bertocci, Peter van Endert, Ren Xu

INNATE AND ADAPTIVE IMMUNE MECHANISMS IN AUTOIMMUNE DIABETES

We are interested in understanding innate and adaptive mechanisms that modulate the pathophysiology of autoimmune type 1 diabetes and in exploiting such mechanisms for prevention and treatment of the disease. In one axis of research, we have found that antimicrobial peptides, small molecules known as part of first line immune defenses at mucosal surfaces, can both contribute to autoimmunity and protect against it depending on tehri cellular source. Having observed how these peptides can modulate intestinal microbiota in a manner protecting against autoimmunity, we develop a novel therapeutic approach based on antimicrobial peptide delivery through engineered bacteria. In a second line of research, we study a beta cell-intrinsic pathway that induces islet regeneration and protection from autoimmune diabetes and that is activated in the absence of insulin-degrading enzyme, a setting that in addition attenuates autoimmune T cell responses against insulin. Finally, we are developing nanoparticles carrying beta cell antigens designed to stimulate B lymphocytes producing cytokines which protect beta cells from autoimmune aggression.

Members of the team

Peter van Endert, PU-PH

Julien Diana, DR INSERM

Barbara Bertocci, CR INSERM

Emmanuelle Waeckel-Énée, IE UPC

Maeva Agapoff, PhD student

Nadia Keelan, PhD student

Ren Xu, M.D., intern

5 main publications

Enée E et al.
ZnT8 is a major CD8+ T cell-recognized autoantigen in pediatric type 1 diabetes.
Diabetes 61 (2012): 1779-84
Miani M, Le Naour J, Waeckel-Énée É, Verma SC, Straube M, van Endert P, Sokol H, Diana J.
Interplay between the gut microbiota and innate lymphoid cells stimulates ß-defensin 14 expression by pancreatic endocrine cells regulating autoimmune diabetes.
Cell Metab. (2018) pii: S1550-4131(18)30394-2. doi: 10.1016/j.cmet.2018.06.012
Diana J et al.
Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes.
Nat. Med. 19 (2013): 65-73
Sun J et al.
Pancreatic beta cells express a cathelicidin-related antimicrobial peptide regulating autoimmune diabetes.
Immunity 43 (2015): 304-17
Van Endert P.
Intracellular recycling and cross-presentation by MHC class I molecules.
Immunol. Rev. 272 (2016): 80-96

Team members

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.