| First Author | Clutter SD | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 1 | Pages | 234-9 |
| PubMed ID | 19109154 | Mgi Jnum | J:143038 |
| Mgi Id | MGI:3822684 | Doi | 10.4049/jimmunol.182.1.234 |
| Citation | Clutter SD, et al. (2009) Follistatin-like protein 1 promotes arthritis by up-regulating IFN-gamma. J Immunol 182(1):234-9 |
| abstractText | Follistatin-like protein-1 (FSTL-1) is a poorly characterized protein that is up-regulated in the early stage of collagen-induced arthritis and that exacerbates arthritis when delivered by gene transfer. The current study was designed to determine the mechanism by which FSTL-1 promotes arthritis. FSTL-1 was injected into mouse paws, resulting in severe paw swelling associated with up-regulation of IFN-gamma transcript and the IFN-gamma-induced chemokine, CXCL10. Mice depleted of T cells were protected. A central role for IFN-gamma was confirmed by the finding that mice deficient in IFN-gamma failed to exhibit paw swelling in response to injection of FSTL-1. Furthermore, IFN-gamma secretion from mouse spleen cells exposed to a weak TCR signal was increased 5-fold in the presence of FSTL-1. FSTL-1 could be induced by innate immune signals, including TLR4 agonists and the arthritogenic cytokine, IL-1beta, via an NFkappaB pathway. Finally, FSTL-1 was found to be overexpressed in human arthritis and its neutralization inhibited murine collagen-induced arthritis and suppressed IFN-gamma and CXCL10 production in arthritic joints. These findings demonstrate that FSTL-1 plays a critical role in arthritis by enhancing IFN-gamma signaling pathways and suggest a mechanism by which FSTL-1 bridges innate and adaptive immune responses. |
