adaptive immunity; CD4 T cells; autoimmunity; antigen presentation; macroautophagy ; rheumatoid arthritis
Niven Jennifer, Madelon Natacha, Page Nicolas, Caruso Assunta, Harlé Guillaume, Lemeille Sylvain, Seemayer Christian A., Hugues Stéphanie, Gannagé Monique (2019), Macroautophagy in Dendritic Cells Controls the Homeostasis and Stability of Regulatory T Cells, in Cell Reports
, 28(1), 21-29.e6.
Gannage Monique, da Silva Rosa Barreira, Münz Christian (2019), Antigen ProcessingMethods and Protocols
, Springer New York, New York, NY.
Dubrot Juan, Duraes Fernanda V, Harlé Guillaume, Schlaeppi Anjalie, Brighouse Dale, Madelon Natacha, Göpfert Christine, Stokar-Regenscheit Nadine, Acha-Orbea Hans, Reith Walter, Gannagé Monique, Hugues Stephanie (2018), Absence of MHC-II expression by lymph node stromal cells results in autoimmunity, in Life Science Alliance
, 1(6), e201800164-e201800164.
Macroautophagy is a major catabolic pathway in the cells, acting in parallel to the proteasome machinery. This pathway is an important contributor of cellular homeostasis, and therefore is active and upregulated in various conditions of cellular stress and inflammation. In this context macroautophagy has been implicated in shaping the innate and adaptive immune responses by acting at multiple and diverse levels such as pathogen clearance, cytokine secretion, and antigen presentation. Our preliminary results indicate that macroautophagy is active and upregulated in arthritic joints during the course of rheumatoid arthritis (RA). I propose to analyze the contribution of macroautophagy in antigen presenting cells to the adaptive immune response during autoimmune arthritis through the following three specific aims:1. Address the consequences of macroautophagy deletion in dendritic cells on peripheral tolerance in the steady state2.Analyze the contribution of macroautophagy in dendritic cells to the adaptive immune response in mouse models of arthritis3. Analyze in human samples the contribution of macroautophagy in dendritic cells to the degradation, citrullination and antigen processing of selected auto-antigens relevant to RA.In summary these studies will determine if macroautophagy contributes to the deregulated immune responses during RA. A better understanding of the role of macroautophagy during autoimmunity and during RA might suggest therapeutic benefits of targeting this pathway.