Abstract
Autophagy, initially viewed as a conserved bulk-degradation mechanism, has emerged as a central player in a multitude of immune functions. Autophagy is important in host defense against intracellular and extracellular pathogens, metabolic syndromes, immune cell homeostasis, antigen processing and presentation, and maintenance of tolerance. The observation that the above processes are implicated in triggering or exacerbating autoimmunity raises the possibility that autophagy is involved in mediating autoimmune processes, either directly or as a consequence of innate or adaptive functions mediated by the pathway. Genome-wide association studies have shown association between single nucleotide polymorphisms (SNPs) in autophagy related gene 5 (Atg5), and Atg16l1 with susceptibility to systemic lupus erythematosus (SLE) and Crohn’s disease, respectively. Enhanced expression of Atg5 was also reported in blood of mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), and in T cells isolated from blood or brain tissues from patients with active relapse of MS. This review explores the roles of autophagy pathway in the innate and adaptive immune systems on regulating or mediating the onset, progression, or exacerbation of autoimmune processes.
Highlights
Autophagy, initially viewed as a conserved bulk-degradation mechanism, has emerged as a central player in a multitude of immune functions
Enhanced expression of autophagy related gene 5 (Atg5) was reported in blood of mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), and in T cells isolated from blood or brain tissues from patients with active relapse of MS
This review explores the roles of autophagy pathway in the innate and adaptive immune systems on regulating or mediating the onset, progression, or exacerbation of autoimmune processes
Summary
Reviewed by: Christian Muenz, University of Zurich, Switzerland Willem Van Eden, Utrecht University, Netherlands. This review explores the roles of autophagy pathway in the innate and adaptive immune systems on regulating or mediating the onset, progression, or exacerbation of autoimmune processes. AUTOPHAGY IN LYMPHOCYTE DEVELOPMENT T cell development in the thymus undergoes positive and negative selections, processes in which extrinsic inputs from thymic epithelial cells (TECs) play a major role in shaping the T cell repertoire. Mice with Atg deficiency in TECs showed severely impaired central tolerance and autoimmune organ destruction, suggesting that autophagy-mediated display of MHC-antigen complex on surface of TECs is essential for proper T cell development (Nedjic et al, 2008). A recent report demonstrated the requirement of autophagy in TECs for loading endogenous antigens onto MHC-II and that this process was essential for negative selections of CD4 T cells (Aichinger et al, 2013). As Tregs are among the major players controlling autoimmunity (La Cava, 2009), this might www.frontiersin.org
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