Follistatin-Like Protein 1 Contributes to Acute Traumatic Spinal Cord Injury by Enhancing Neuroinflammation Through the Modulation of Interferon Regulatory Factor 5-Mediated Macrophage Activation

Background and Purpose: Follistatin-like protein 1 (Fstl1) is a secreted glycoprotein with context-dependent inflammatory activity. We investigated whether Fstl1 is a reproducible feature of traumatic spinal cord injury (SCI) and whether it regulates macrophage activation through interferon regulatory factor 5 (IRF5).

Methods

A target-blind analysis integrated four public SCI bulk transcriptomic cohorts with single-cell and spatial datasets. Findings were tested in wild-type and Fstl1+/− mice after SCI using spinal cord RNA sequencing, molecular and histological assays, behavioral testing, and bone marrow-derived macrophages with IRF5 gain- and loss-of-function. Adult-induced Postn-CreER-mediated Fstl1 deletion was evaluated in fibroblast–macrophage non-contact co-cultures.