Monique Gannage, Jennifer Niven and Assunta Caruso
University of Geneva, Switzerland
University Hospital, Switzerland
Posters & Accepted Abstracts: Immunome Res
Macroautophagy is a major catabolic pathway, acting in parallel to the proteasome machinery. It is an important contributor of cellular homeostasis and therefore is active and up-regulated in various conditions of stress and inflammation. Macroautophagy has been implicated in shaping the innate and adaptive immune responses by acting at multiple and diverse levels including cytokine secretion and antigen presentation. We analyzed the contribution of macroautophagy in dendritic cells (DCs), to the immune response in the antigen induced arthritis mice model. We used mice that are deficient in autophagy in their dendritic cells by crossing the CD11c-Cre mice to Atg5flox/flox mice. ATG5 is an essential autophagy gene and its targeted deletion in dendritic cells completely abolished a functional autophagy pathway in DCs. We found that mice lacking autophagy in their DCs (DC/ATG5-/-) showed enhanced cartilage destruction and bone erosion. Interestingly, the Th1/Th17 response in (DC/ATG5-/-) mice was significantly increased, assessed through enhanced INF-gamma and IL-17 production. Furthermore, in vitro, BMDC from DC/ATG5-/- mice showed an enhanced IL-1├?┬▓ production and an increased expression of co-stimulatory molecule in response to TLR activation. We could further show in vitro that DC/ATG5-/- were capable of priming na├?┬»ve cells towards Th17 more efficiently than wild type DCs. Our results identify a new contribution of macroautophagy as a negative regulator of the immune response during a mice model of autoimmune arthritis. Further investigations will address if manipulating autophagy could change the course of autoimmune arthritis.
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