TGF-[beta] signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 31; p. 10865
• Main Authors: Laouar, Yasmina, Town, Terrence, Jeng, David, Tran, Elise, Wan, Yisong, Kuchroo, Vijay K, Flavell, Richard A
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 05.08.2008
• Subjects: Cells; Encephalitis; Rodents; Studies; T cell receptors; Transgenic animals
• ISSN: 0027-8424; 1091-6490

One unresolved issue in immune tolerance is what prevents self-reactive T cells from activation. In this study, we used a transgenic mouse model of targeted functional inactivation of TGF-βR signaling in CD11c... cells (CD11... mice) and showed a direct impact on the development of experimental autoimmune encephalomyelitis (EAE). We found that MOG... immunization of CD11... mice results in strong inflammation of CNS, high frequency of T cells in CNS, increased levels of T helper 1(T...1) and T...17 cytokines in the periphery, and lack of remission from EAE. Once crossed with mice prone to autoimmunity, double-transgenic CD11c...Mog... mice revealed a spontaneous EAE-like disease characterized by early infiltration of activated myelin-specific T cells into CNS, activation of microglial cells, inflammation of CNS, dysfunction of locomotion, and premature death. We constructed chimeric mice and demonstrated that inactivation of TGF-βR signaling in dendritic cells (DCs) results in augmented EAE-associated T cell responses. Our data provide direct evidence that TGF-β can control autoimmunity via actions on DCs. (ProQuest: ... denotes formulae/symbols omitted.)