IGFBPL1 is a master driver of microglia homeostasis and resolution of neuroinflammation in glaucoma and brain tauopathy

• DOI: 10.1016/j.celrep.2023.112889
• Publication Date: 2023-07-31T09:13:34Z
• Authors: Li Pan; Kin-Sang Cho; Xin Wei; Fuyi Xu; Anton Lennikov; Guangan Hu; Jing Tang; Shuai Guo; Julie Chen; Emil Kriukov; Robert Kyle; Farris Elzaridi; Shuhong Jiang; Pierre A. Dromel; Michael Young; Petr Baranov; Chi-Wai Do; Robert W. Williams; Jianzhu Chen; Lu Lu; Dong Feng Chen
• Keywords: Tauopathy

Microglia shift toward an inflammatory phenotype during aging that is thought to exacerbate age-related neurodegeneration. The molecular and cellular signals resolve neuroinflammation post-injury are largely undefined. Here, we exploit systems genetics methods based on the extended BXD murine reference family identify IGFBPL1 as upstream cis-regulator of microglia-specific genes switch off inflammation. expressed by mouse human microglia, higher levels its expression lipopolysaccharide-induced resetting transcriptome signature back a homeostatic state via IGF1R signaling. Conversely, deficiency or selective deletion in microglia shifts these cells landscape induces early manifestation brain tauopathy retinal Therapeutic administration drives pro-homeostatic prevents glaucomatous neurodegeneration vision loss mice. These results master driver counter-inflammatory microglial modulator presents endogenous resolution prevent eye brain.