ASK1 signaling regulates phase-specific glial interactions during neuroinflammation
Xiaoli Guo, Atsuko Kimura, Kazuhiko Namekata, Chikako Harada, Nobutaka Arai, Kohsuke Takeda, Hidenori Ichijo, Takayuki Harada
Abstract
system, and we found that ASK1 signaling in microglia played a major role in generating and maintaining disease. Activated astrocytes produce key inflammatory mediators, including CCL2, that further activated and recruited microglia/macrophages, in an astrocytic ASK1-dependent manner. Astrocyte-specific analysis revealed CCL2 expression was higher in the later stage compared with the early stage, suggesting a greater proinflammatory role of astrocytes in the later stage. Our findings demonstrate cell-type-specific roles of ASK1 and suggest phase-specific ASK1-dependent glial cell interactions in EAE pathophysiology. We propose glial ASK1 as a promising therapeutic target for reducing neuroinflammation.