| First Author | Zheng Y | Year | 2023 |
| Journal | FASEB J | Volume | 37 |
| Issue | 4 | Pages | e22833 |
| PubMed ID | 36921064 | Mgi Jnum | J:341946 |
| Mgi Id | MGI:7537093 | Doi | 10.1096/fj.202201767R |
| Citation | Zheng Y, et al. (2023) Blocking the IFN-gamma signal in the choroid plexus confers resistance to experimental autoimmune encephalomyelitis. FASEB J 37(4):e22833 |
| abstractText | Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). IFN-gamma (IFN-gamma), a critically important immunomodulator, has been widely studied in MS pathology. The confusing and complex effects of IFN-gamma 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-gamma signaling in the choroid plexus (CP) in the experimental autoimmune encephalomyelitis (EAE) model. We found that the IFN-gamma 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-gamma signal via knockdown of IFN-gammaR1 in the CP could protect mice against EAE pathology, as evidenced by improvements in clinical scores and infiltration. Notably, knocking down IFN-gammaR1 in the CP reduced the local expression of adhesion molecules and chemokines. This finding suggests that IFN-gamma 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-gamma signaling between peripheral lymphocytes and the choroid plexus may determine whether IFN-gamma has a protective or aggravating effect on EAE pathology. Above all, we discovered that IFN-gammaR1-mediated IFN-gamma signaling in the CP was a vital pathway in the pathological process of EAE. |
