@article{243de633e5ec4fdcb5a6ec7a1db38d41,
title = "Microglia promote autoimmune inflammation via the noncanonical NF-κB pathway",
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.",
author = "Zuliang Jie and Ko, {Chun Jung} and Hui Wang and Xiaoping Xie and Yanchuan Li and Meidi Gu and Lele Zhu and Yang, {Jin Young} and Tianxiao Gao and Wenjuan Ru and Tang, {Shao Jun} and Xuhong Cheng and Sun, {Shao Cong}",
note = "Funding Information: We thank Genentech Inc. for providing Map3k14 flox mice, Walter and Eliza Hall Institute of Medical Research for Nfkb2Lym1 mice, and R Brink for Traf3 flox mice. We also thank the flow cytometry and animal facility of the shared resources at the MD Anderson Cancer Center, supported by the NIH/NCI Cancer Center Support Grant (CCSG) P30CA016672. This study was supported by NIH grant GM84459 to S.-C.S. and partially supported by NIH grant NS079166 to S.-J.T. T.G. was a visiting student supported by a scholarship from the China Scholarship Council with the grant number of 201906380080. Publisher Copyright: {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",
year = "2021",
month = sep,
doi = "10.1126/sciadv.abh0609",
language = "English (US)",
volume = "7",
journal = "Sci Adv",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "36",
}