Autophagy comprises a growing range of cellular pathways, which occupy central roles in response to energy deprivation, organelle turnover and proteostasis. Over the years, autophagy has been increasingly linked to governing several aspects of immunity, including host defence against various pathogens, unconventional secretion of
cytokines and antigen presentation. While canonical autophagy-mediated antigen processing in thymic epithelial cells supports the generation of a self-tolerant CD4+ T cell repertoire, mounting evidence suggests that deregulated autophagy pathways contribute to or sustain autoimmune responses. In animal models of
multiple sclerosis (MS), non-canonical autophagy pathways such as
microtubule-associated protein 1 A/1 B-light chain 3 (LC3)-associated phagocytosis can contribute to major histocompatibility complex (MHC) class II presentation of
autoantigen, thereby amplifying autoreactive CD4+ T cell responses. In
systemic lupus erythematosus (SLE), increased type 1
interferon production is linked to excessive autophagy in plasmacytoid dendritic cells (DCs). In
rheumatoid arthritis (RA), autophagy
proteins contribute to pathological citrullination of
autoantigen.
Immunotherapies effective in
autoimmune diseases modulate autophagy functions, and strategies harnessing autophagy pathways to restrain autoimmune responses have been developed. This review illustrates recent insights in how autophagy, distinct autophagy pathways and autophagy
protein functions intersect with the evolution and progression of
autoimmune diseases, focusing on MS, SLE and RA.