Microglia promote autoimmune inflammation via the noncanonical NF-κB pathway
Zuliang Jie, Chun‐Jung Ko, Hui Wang, Xiaoping Xie, Yanchuan Li, Meidi Gu, Lele Zhu, Jin‐Young Yang, Tianxiao Gao, Wenjuan Ru, Shao‐Jun Tang, Xuhong Cheng, Shao‐Cong Sun
Abstract
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-κB) pathway. Microglia-specific deletion of the noncanonical NF-κB-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-κB 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.