Follistatin-like protein 1 modulates IL-17 signaling via IL-17RC regulation in stromal cells

Follistatin-like protein 1 (FSTL-1) possesses several newly identified roles in mammalian biology, including IL-17 driven inflammation, though the mechanism underlying FSTL-1 influence on IL-17 mediated cytokine production is unknown. Using parallel in vitro bone marrow stromal cell models of FSTL-1 suppression we employed unbiased microarray analysis to identify FSTL-1 regulated genes and pathways that could influence IL-17 dependent production of IL-6 and G-CSF. We discovered that FSTL-1 modulates Il17rc gene expression. Specifically, FSTL-1 was necessary for Il17rc gene transcription, IL-17RC surface protein expression and IL-17-dependent cytokine production. This work identifies a mechanism by which FSTL-1 influences IL-17 driven inflammatory signaling in vitro and reveals a novel function for FSTL-1, as a modulator of gene expression. Thus, enhanced understanding of the interplay between FSTL-1 and IL-17 mediated inflammation may provide insight into potential therapeutic targets of IL-17 mediated diseases and warrants ongoing study of in vivo models and clinical scenarios of FSTL-1-influenced diseases.