Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). IFN-gamma (IFN-γ), a critically important immunomodulator, has been widely studied in MS pathology. The confusing and complex effects of IFN-γ in MS patients and rodent models, however, cause us to look more closely at its exact role in MS. In this study, we identified the role of the IFN-γ signaling in the choroid plexus (CP) in the experimental autoimmune encephalomyelitis (EAE) model. We found that the IFN-γ signal was rapidly amplified when CNS immune cell infiltration occurred in the CP during the progressive stage. Furthermore, using two CP-specific knockdown strategies, we demonstrated that blocking the IFN-γ signal via knockdown of IFN-γR1 in the CP could protect mice against EAE pathology, as evidenced by improvements in clinical scores and infiltration. Notably, knocking down IFN-γR1 in the CP reduced the local expression of adhesion molecules and chemokines. This finding suggests that IFN-γ signaling in the CP may participate in the pathological process of EAE by preventing pathological T helper (Th) 17 + cells from infiltrating into the CNS. Finally, we showed that the unbalanced state of IFN-γ signaling between peripheral lymphocytes and the choroid plexus may determine whether IFN-γ has a protective or aggravating effect on EAE pathology. Above all, we discovered that IFN-γR1-mediated IFN-γ signaling in the CP was a vital pathway in the pathological process of EAE.
Home>Blocking the IFN-gamma signal in the choroid plexus confers resistance to experimental autoimmune encephalomyelitis
Blocking the IFN-gamma signal in the choroid plexus confers resistance to experimental autoimmune encephalomyelitis
- Impact factors: 7
- Publication: Journal of Animal Science and Biotechnology
- Author:Ma Xinhao, Yang Xinran, Zhang Dianqi, Zhang Wenzhen, Wang Xiaoyu, Xie Kuncheng, He Jie, Mei Chugang, Zan Linsen
- DOI citation-doi:10.1186/s40104-022-00820-1
- Date:2023-02-03T00:00:00.000Z