ATG-dependent phagocytosis in dendritic cells drives myelin-specific CD4 + T cell pathogenicity during CNS inflammation

• DOI: 10.1073/pnas.1713664114
• Publication Date: 2017-12-12T18:43:13Z
• Authors: Christian W. Keller; Christina Sina; Monika B. Kotur; Giulia Ramelli; Sarah Mundt; Isaak Quast; Laure-Anne Ligeon; Patrick Weber; Burkhard Becher; Christian Münz; Jan D. Lünemann
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; 1000 Multidisciplinary; Encephalomyelitis, Autoimmune, Experimental; 610 Medicine & health; Mice, Transgenic; Dendritic Cells; 10263 Institute of Experimental Immunology; Autophagy-Related Protein 5; 3. Good health; Mice; 03 medical and health sciences; Phagocytosis; 570 Life sciences; biology; Animals; Myelin Sheath

Significance How autoreactive CD4 + T cells recognize their target antigen and induce sustained inflammation in organ-specific autoimmune diseases is incompletely understood. In an experimental model of multiple sclerosis, we show that accumulation myelin-specific within the CNS subsequent clinical disease development requires autophagy protein (ATG)-dependent phagocytosis dendritic (DCs). Absence ATG-dependent DCs abrogates myelin presentation to following oligodendroglial cells, its pharmacological inhibition delays onset reduces severity encephalomyelitis. Thus, use for enhanced during inflammation, thereby linking oligodendrocyte injury with processing cell pathogenicity.