Heming, J.-N.; Margraf, A.; Najder, K.; Germena, G.; Richter, M.; Cappenberg, A.; Henke, K.; Bardel, B.; Schemmelmann, L.; Oguama, M.; Lindental, P.; Amini, W.; Sobocik, J.; Schett, G.; Krönke, G.; Block, H.; Rossaint, J.; Soehnlein, O.; Zarbock, A.
Abstract
Neutrophils play a key role in autoimmune diseases like rheumatoid arthritis, contributing to tissue damage through rapid recruitment and activation. In this study, we investigated the regulatory properties of two receptor-like tyrosine phosphatases (RPTPs), CD45 and CD148, in inflammatory arthritis. Using an in vivo mouse model of K/BxN serum transfer-induced arthritis, we found that CD45 and CD148 feature distinct regulatory properties during inflammatory arthritis. CD45 is required for neutrophil infiltration, cytokine release, and reactive oxygen species production, whereas CD148 deficiency leads to a delayed onset of arthritis but unaltered overall neutrophil infiltration and reduced ROS production. Furthermore, we could demonstrate that activation of Src family kinases in neutrophils is differentially regulated by CD45 and CD148 in a stimulus-dependent manner. Summarizing, our results suggest that CD45 is positively involved, while CD148 is positively and negatively involved in neutrophil recruitment and function during inflammatory arthritis.
Keywords: Src family kinases; arthritis; integrins; neutrophil recruitment; neutrophils.