Open AccessPathogenic TNF-α drives peripheral nerve inflammation in an Aire-deficient model of autoimmunity
Author(s) -
Yan Wang,
Lily Guo,
Xihui Yin,
Ethan C McCarthy,
Mandy I. Cheng,
Aline Hoang,
Ho-Chung Chen,
Anushi Patel,
Denise Allard Trout,
Erin Xu,
Natalie Yakobian,
Willy Hugo,
James F. Howard,
Katherine M. Sheu,
Alexander Hoffmann,
Melissa G. Lechner,
Maureen A. Su
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2114406119
Subject(s) - immunology , autoimmunity , tumor necrosis factor alpha , immune system , proinflammatory cytokine , inflammation , biology , macrophage polarization , medicine , macrophage , biochemistry , in vitro
Significance GBS and CIDP are autoimmune disorders of the PNS that can be debilitating and even life threatening. Current therapies, which include corticosteroids and intravenous gammaglobulin, have poorly defined mechanisms of action and are ineffective in a fraction of patients. To identify more specific therapeutic targets, we used single-cell RNA sequencing to analyze immune cells in nerves during autoimmune attack. This analysis revealed a previously unappreciated TNFα cell–cell communication pathway that recruits and activates multiple immune cell types. Moreover, we show that TNF-α signaling is an essential feature of PNS autoimmunity, since ablating TNF-α signaling protects against disease. These findings suggest that anti–TNF-α agents, which are already used to treat other inflammatory diseases, should be considered for inflammatory neuropathies.