Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins

Cadwell, Ken; Debnath, Jayanta

RA is an autoimmune disease that primarily affects the joints and is associated with the presence of autoantibodies that are reactive to citrullinated peptides that are presented by MHC-II molecules. In contrast to IBD, ATG function may promote RA. ATG5 is required for generation of citrullinated antigens by peptidylarginine deiminases, potentially by mediating the trafficking of these enzymes to MHC-II antigen loading compartments (Ireland and Unanue, 2011) . CTLA4 on anti-inflammatory T cells binds B7 molecules on dendritic cells to inhibit LC3 expression and autophagy, which dampens the capacity to present antigens (Alissafi et al., 2017) . The CTLA4-Ig fusion molecule abatacept, which is used to treat RA, also inhibits ATG-mediated antigen presentation by dendritic cells, suggesting that dampening autophagy is part of the mechanism of action of this drug (Alissafi et al., 2017) . Because it is currently unclear when autophagy or an autophagy-related process such as LAP mediates antigen presentation, an important future direction will be to determine which ATGs are necessary for autoantigen presentation, and whether this differs among cell types.