Adaptive immunity at the crossroads of autophagy and metabolism

Abstract

The function of lymphocytes is dependent on their plasticity, particularly their adaptation to energy availability and environmental stress, and their protein synthesis machinery. Lymphocytes are constantly under metabolic stress, and macroautophagy/autophagy is the primary metabolic pathway that helps cells overcome stressors. The intrinsic role of autophagy in regulating the metabolism of adaptive immune cells has recently gained increasing attention. In this review, we summarize and discuss the versatile roles of autophagy in regulating cellular metabolism and the implications of autophagy for immune cell function and fate, especially for T and B lymphocytes.

Keywords: Immunology; Lysosome; Macroautophagy; Stress.

Fig. 1

Overview of autophagy. Macroautophagy is initiated by the ULK1 and PIK3C3/Vps34 complexes, which trigger the nucleation of the phagophore at the omegasome. The membrane sources required for phagophore biogenesis are supplied by ATG9-containing vesicles and phospholipids channeled from the ER into the growing phagophore by the ATG2-WDR45/WIPI4 complex. Two ubiquitin-like conjugation systems facilitate phagophore expansion and closure. Subsequently, the autophagosome fuses with the lysosome, where its contents are degraded, and the macromolecules thus generated are recycled.