Pathogenic TNF-α drives peripheral nerve inflammation in an Aire-deficient model of autoimmunity

Abstract

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.