Multiple regulatory and effector roles of autophagy in immunity.
Autophagy is a cytoplasmic homeostasis pathway, enabling cells to digest their own cytosol, remove toxic protein aggregates, and eliminate defective or surplus organelles. A plenitude of studies has now expanded roles of autophagy to both effector and regulatory functions in innate and adaptive immunity. In its role of an immunological effector, autophagy plays many parts: (i) In its most primeval manifestation, it captures and digests intracellular microbes, (ii) it is an antimicrobial output of Toll-like receptor (TLR) response to pathogen associated molecular patterns (PAMP), and (iii) it is an effector of Th1-Th2 polarization in resistance or susceptibility to intracellular pathogens. As a regulator of immunity, autophagy plays a multitude of functions: (i) It acts as a topological inversion device servicing both innate and adaptive immunity by delivering cytosolic antigens to the lumen of MHC II compartments and cytosolic PAMPs to endosomal TLRs, (ii) it is crucial in T cell repertoire selection in the thymus and control of central tolerance, (iii) it plays a role in T and B cell homeostasis, and (iv) it is of significance for inflammatory pathology. A properly functioning autophagy helps prevent autoimmunity and assists in clearing pathogens. When aberrant, it contributes to human inflammatory disorders such as Crohn's disease.
Deretic
Vojo
V
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, 87131, USA. vderetic@salud.unm.edu
D000818:Animals; D017951:Antigen Presentation; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D000071183:Autophagy-Related Proteins; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007108:Immune Tolerance; D007239:Infections / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D051193:Toll-Like Receptors