Extracellular matrix protein 1 (ECM1) is an 85-kDa glycoprotein which plays a key role in malignancies, tumor progression, angiogenesis and skin physiology. Previous studies demonstrated that ECM1 is specifically secreted by T helper type 2 (Th2) cells and promotes their egress from draining lymph nodes in an animal model of asthma. However, the regulatory effect of ECM1 on immune system and its function during myelin-oligodendrocyte-glycoprotein-induced (MOG-induced) Experimental autoimmune encephalomyelitis (EAE) remain unknown.

Recently, a team of researchers led by Prof. SUN Bing at Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS) of Chinese Academy of Sciences (CAS) found a novel function of ECM1 in inhibiting T helper type 17 (Th17) differentiation in the EAE model, suggesting that ECM1 may have a potential to be used in clinical applications for understanding the pathogenesis of Multiple sclerosis (MS) and its diagnosis. This study was published in The Journal of Immunology.

Th17 cells are important to disease induction, while Th2 cells are inhibitory in the disease progression. In the study, researchers reported the effect of a Th2 cell product, ECM1, on the differentiation of Th17 cells and the development of EAE. Their investigation observed that ECM1 administration from day one to day seven following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo.

Further mechanism study revealed that ECM1 could interact with αv integrin on dendritic cell (DC) cells and suppress the αv integrin-mediated activation of latent transforming growth factor-beta (TGF-β). As a result, the differentiation of Th17 at early stage of EAE induction was inhibited. Moreover, overexpression of ECM1 in vivo significantly suppresses Th17 cell response and attenuates EAE induction in ECM1 transgenic mouse.

This study contributes to a deeper understanding of the pathogenesis of human multiple sclerosis (MS). In addition, the identification of ECM1 as an inhibitor of Th17 development may provide a potential therapeutic approach in Th17 cell-mediated diseases.

Prof. SUN Bing conducted the work in collaboration with Prof. ZHU Jinfang’s lab from National Institute of Allergy and Infectious Diseases and Prof. WU Zhiying’s lab from Zhejiang University School of Medicine.

This work was supported by the National Natural Science Foundation of China, National 973 key project, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, USA and NN-CAS foundation.