Noncanonical autophagy in dendritic cells triggers CNS autoimmunity |
| |
Authors: | Christian W. Keller |
| |
Affiliation: | Institute of Experimental Immunology, Department of Neuroinflammation, University Hospital of Zurich, Zurich, Switzerland |
| |
Abstract: | Reactivation and expansion of myelin-reactive CD4+ T cells within the central nervous system (CNS) are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We demonstrated that accumulation of myelin-specific CD4+ T cells within the CNS and subsequent clinical disease development require autophagy related (ATG) protein-dependent phagocytosis in dendritic cells (DCs). Genetic ablation of this pathway impairs presentation of myelin-associated antigen following phagocytosis of injured, phosphatidylserine-exposing oligodendroglial cells. Thus, DCs use ATG-dependent phagocytosis for enhanced presentation of myelin antigen, thereby linking oligodendrocyte injury with antigen processing and T cell-pathogenicity during autoimmune CNS inflammation. |
| |
Keywords: | autophagy EAE multiple sclerosis neuroinflammation phagocytosis |
|
|