Autophagy is a vital catabolic process for degrading bulky cytosolic contents, which cannot be resorbed via the proteasome. First described as a survival mechanism during nutrient starvation conditions, recent reports have demonstrated that autophagy supports metabolic functions of T cells at various stages of maturation and effector function. Autophagy is crucial for T-cell development at the precursor stage as self-renewability and quiescence of hematopoietic stem cells depend on autophagy of the mitochondria and the endoplasmic reticulum. Later, during development in the thymus, autophagy regulates peptide presentation in stromal cells and professional antigen-presenting cells, which mediate thymocyte selection. Furthermore, the metabolic changes when mature T cells enter the periphery and when they are activated are both dependent on autophagy. Lastly, autophagy prevents early aging and, thus, ensures maintenance of memory T cells. Autophagy is an eukaryotic, cytoplasmic (self-)recycling process, in which proteins as well as entire organelles are degraded via lysosomes. There are three different types of autophagy, namely chaperonemediated autophagy, microautophagy and macroautophagy. Chaperone-mediated autophagy, unlike the other two types of autophagy, only degrades soluble cytosolic proteins by directly transferring heat-shock cognate protein of 70 kDa-tagged proteins across the lysosomal membrane. 1 Both micro-and macroautophagy can be nonselective as well as specific in their cargo selection and both are capable of degrading large-sized molecules. During microautophagy, the lysosomal membrane invaginates to sequester cytosolic content directly. 2 Macroautophagy is distinct, in that a doublemembrane structure, the autophagosome, is formed around its cytosolic cargo. This is also the most well-studied type of autophagy, and as this review deals with macroautophagy, it will be referred to simply as 'autophagy' hereafter.Autophagy is essential for degradation of aggregated proteins (aggrephagy) 3 and damaged organelles including mitochondria (mitophagy), peroxisomes (pexophagy) and ER (ERphagy). These were previously reviewed in Ding and Yin, 4 Sakai et al. 5 and Bernales et al., 6 respectively. As autophagy is a fundamental process needed by almost all cell types to maintain cell homeostasis, a basal level of autophagy occurs constantly. 7 Beyond this, autophagy is vital for cells during stress conditions such as starvation, activation, growth and proliferation, to provide cells with essential metabolic intermediates. These basic autophagic functions are relevant in diseases as well as aging, as the accumulation of aggregated proteins, damaged organelles or other molecules is an underlying problem of many diseases. For instance, autophagy has been implicated in neurodegenerative diseases, 8,9 Crohn's disease, 10,11 cancer, 12,13 aging 4,15 and cystic fibrosis, 16 as well as metabolic-related diseases such as fatty liver (macrolipophagy), 17 autophagic vacuolar myopathies (glycogen degradation) 18,19 and di...

Autophagy is an evolutionary conserved catabolic pathway that ensures the degradation of intracellular components. The autophagic pathway is regulated by autophagy-related (Atg) proteins that govern formation of double-membraned vesicles called autophagosomes. Autophagy deficiency in regulatory T (Treg) cells leads to increased apoptosis of these cells and to the development of autoimmune disorders, predominantly characterized by intestinal inflammation. Recently, RORγt-expressing Treg cells have been identified as key regulators of gut homeostasis, preventing intestinal immunopathology. To study the role of autophagy in RORγt+ Foxp3+ Treg cells, we generated mice lacking the essential component of the core autophagy machinery Atg5 in Foxp3+ cells. Atg5 deficiency in Treg cells led to a predominant intestinal inflammation. While Atg5-deficient Treg cells were reduced in peripheral lymphoid organs, the intestinal RORγt+ Foxp3+ subpopulation of Treg cells was most severely affected. Our data indicated that autophagy is essential to maintain the intestinal RORγt+ Foxp3+ Treg population, thereby protecting the mice from gut inflammatory disorders.