Innate and adaptive immune pathways in autoimmunity and auto-inflammation

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