title: Deficiency of autophagy in dendritic cells protects against experimental autoimmune encephalomyelitis.
abstract: Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in the immune system. DCs present antigens to CD8 and CD4 T cells in the context of class I or II MHC. Recent evidence suggests that autophagy, a conserved intracellular degradation pathway, regulates class II antigen presentation. In vitro studies have shown that deletion of autophagy-related genes reduced antigen presentation by APCs to CD4 T cells. In vivo studies confirmed these findings in the context of infectious diseases. However, the relevance of autophagy-mediated antigen presentation in autoimmunity remains to be elucidated. Here, we report that loss of autophagy-related gene 7 (Atg7) in DCs ameliorated experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-mediated mouse model of multiple sclerosis, by reducing in vivo priming of T cells. In contrast, severity of hapten-induced contact hypersensitivity, in which CD8 T cells and NK cells play major roles, was unaffected. Administration of the autophagy-lysosomal inhibitor chloroquine, before EAE onset, delayed disease progression and, when administered after the onset, reduced disease severity. Our data show that autophagy is required in DCs for induction of EAE and suggest that autophagy might be a potential target for treating CD4 T cell-mediated autoimmune conditions.
authors: Departments of Medicine and Baylor College of Medicine, Houston, Texas 77030; Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 77030.
authors: Abhisek
authors: A
authors: Bhattacharya
authors: Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 77030.
authors: Xyanthine
authors: X
authors: Parillon
authors: Departments of Medicine and Baylor College of Medicine, Houston, Texas 77030.
authors: Shenyan
authors: S
authors: Zeng
authors: Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 77030.
authors: Shuhua
authors: S
authors: Han
authors: Departments of Medicine and Baylor College of Medicine, Houston, Texas 77030; Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 77030. Electronic address: teissa@bcm.edu.
authors: N Tony
authors: NT
authors: Eissa
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001343:Autophagy / Q000187:drug effects; D000071193:Autophagy-Related Protein 7; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D002738:Chloroquine; D000071193:Autophagy-Related Protein 7
keywords: Antigen Presentation; Autoimmunity; Autophagy; Autophagy-related Protein 7 (ATG7); Dendritic Cell; Multiple Sclerosis