Extracellular matrix protein 1 plays a critical role in driving Th2 cell migration and controlling Th17 cell differentiation (IRC7P.434)

Abstract

Abstract Abstract: Extra-Cellular Matrix Protein 1 (ECM1), a secreted protein, is highly and selectively expressed in Th2 cells. ECM1 deficiency caused impaired Th2 responses and reduced allergic airway inflammation in vivo. Functional analysis demonstrated that ECM1 deficient Th2 cells exhibited a defect in migration and were retained in peripheral lymphoid organs. Based on the cross-inhibition between Th2 and Th1/Th17 cells, we discovered a novel function of ECM1 in ameliorating Experimental autoimmune encephalomyelitis (EAE) which is mediated by Th1/Th17 cells. After the recombinant ECM1 were administrated i.v during EAE induction, the development of Th17 cells was decreased. In mechanism study we found that ECM1 could interact with integrin αv and block the interaction of integrin αv and latent TGF-β, which is critically for activating latent TGF-β maturation and then consequently to determine Th17 cell differentiation. To confirm the novel function of endogenous ECM1 in vivo, ecm1 transgenic mice was used to induce EAE. The data showed that EAE induction was suppressed significantly as compared with control group, which was associated with the failure of Th17 cell development. Our clinical observation indicated that ECM1 function is correlated with the pathogenesis of MS. This discovery offers new concept that ECM1 has potential in clinical application for understanding the pathogenesis of MS and its diagnosis.