Search

The interactions of fibroblast-like synoviocyte (FLS)-derived pro-inflammatory cytokines/chemokines and immune cells support the recruitment and activation of inflammatory cells in RA. Here, we show for the first time that the classical myokine myostatin (GDF-8) is involved in the recruitment of Th17 cells to inflammatory sites thereby regulating joint inflammation in a mouse model of TNFalpha-mediated chronic arthritis. Mechanistically, myostatin-deficiency leads to decreased levels of the chemokine CCL20 which is associated with less infiltration of Th17 cells into the inflamed joints. In vitro, myostatin alone or in combination with IL-17A enhances the secretion of CCL20 by FLS whereas myostatin-deficiency reduces CCL20 secretion, associated with an altered transmigration of Th17 cells. Thus, the communication between activated FLS and Th17 cells through myostatin and IL-17A may likely contribute to a vicious cycle of inflammation, accounting for the persistence of joint inflammation in chronic arthritis. Blockade of the CCL20–CCR6 axis by inhibition of myostatin may, therefore, be a promising treatment option for chronic inflammatory diseases such as arthritis., Finanziert über die DEAL-Vereinbarung mit Wiley 2019-2022.

Synovial fibroblast stimulation with activin A; increasing suppression of follistatin release through RASF by activin A concentrations of 0.5 ng/ml and higher (n = 3, experimental replicates). (PPT 220 kb)

Western blot confirmed the presence of the ACVR2A receptor on RASF, which was not altered by different concentrations of activin A (10 to 30â ng/ml) after 15 h stimulation. (PPT 134 kb)