| First Author | Jie Z | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 36 | Pages | eabh0609 |
| PubMed ID | 34516909 | Mgi Jnum | J:367318 |
| Mgi Id | MGI:6766282 | Doi | 10.1126/sciadv.abh0609 |
| Citation | Jie Z, et al. (2021) Microglia promote autoimmune inflammation via the noncanonical NF-kappaB pathway. Sci Adv 7(36):eabh0609 |
| abstractText | Microglia have been implicated in neuroinflammatory diseases, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). We demonstrate that microglia mediate EAE disease progression via a mechanism relying on the noncanonical nuclear factor kB (NF-����B) pathway. Microglia-specific deletion of the noncanonical NF-����B-inducing kinase (NIK) impairs EAE disease progression. Although microglial NIK is dispensable for the initial phase of T cell infiltration into the central nervous system (CNS) and EAE disease onset, it is critical for the subsequent CNS recruitment of inflammatory T cells and monocytes. Our data suggest that following their initial CNS infiltration, T cells activate the microglial noncanonical NF-����B pathway, which synergizes with the T cell-derived cytokine granulocyte-macrophage colony-stimulating factor to induce expression of chemokines involved in the second-wave of T cell recruitment and disease progression. These findings highlight a mechanism of microglial function that is dependent on NIK signaling and required for EAE disease progression. |
