Biography: 

Michel Desjardins completed his PhD at Université de Montréal in 1991. After a postdoctoral fellowship at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, he joined the Department of Pathology and Cell Biology at Université de Montréal (1994) where he is currently a full professor. He has a major interest in cellular pathways associated with the immune system, and has made important contributions to the fields of phagocytosis and antigen cross-presentation. His current research focuses on the role of the immune system in Parkinson’s disease, exploring the proposal that autoimmune mechanisms actively drive the disease process. He is a Fellow of the Royal Society of Canada.

Abstract: 

Emerging evidence identify the immune system as a key player in the pathophysiological process leading to Parkinson’s disease (PD). While it is widely accepted that innate immunity (inflammation) is a key factor in the disease, the contribution of the second arm of the immune system, adaptive immunity, is still being questioned. We have shown previously, both in vitro and in vivo, that the PD proteins PINK1 and Parkin regulate the engagement of an adaptive immune response during inflammation. Indeed, in the absence of PINK1, autoimmune mechanisms are initiated in inflammatory conditions by the presentation of mitochondrial antigens (MitAP) at the surface of antigen-presenting cells. The presentation of these antigens, which activates CD8+ T cells displaying a cytotoxic activity towards dopaminergic neurons, leads to the development of motor impairment in PINK1-/- mice after a gut infection with Gram-negative bacteria. These data led us to propose that autoimmune mechanisms play a key role in the pathophysiological process leading to PD. Characterization of the molecular mechanisms regulating MitAP revealed that the transition from innate (inflammation) to adaptive immunity (antigen presentation) occurs through a complex pathway where the Toll-like receptor 4, cGAS-STING and the unfolded protein response (UPR) are triggered sequentially. Remarkably, we found that LRRK2 is required for the activation of the UPR in inflammatory conditions. Failure to activate the UPR in RAW macrophages lacking LRRK2 results in a significant inhibition of MitAP.  Interestingly, the UPR plays a key role in Crohn’s disease, which is also linked to LRRK2 dysfunction. These data suggest that the UPR is a key step to target in order to limit the engagement of autoimmune mechanisms that may contribute to PD.