Autophagy: An Emerging Immunological Paradigm

Autophagy is a fundamental eukaryotic process with multiple cytoplasmic homeostatic roles, recently expanded to include unique stand-alone immunological functions and interactions with nearly all parts of the immune system. In this article, we review this growing repertoire of autophagy roles in innate and adaptive immunity and inflammation. Its unique functions include cell-autonomous elimination of intracellular microbes facilitated by specific receptors. Other intersections of autophagy with immune processes encompass effects on inflammasome activation and secretion of its substrates, including IL-1β, effector and regulatory interactions with TLRs and Nod-like receptors, Ag presentation, naive T cell repertoire selection, and mature T cell development and homeostasis. Genome-wide association studies in human populations strongly implicate autophagy in chronic inflammatory disease and autoimmune disorders. Collectively, the unique features of autophagy as an immunological process and its contributions to other arms of the immune system represent a new immunological paradigm.