Recently, a research article from Dr. Wang Honglin’s group (Shanghai Jiao Tong University School of Medicine/Shanghai Institute of Immunology) was published online in the journal Stem Cells Translational Medicine. The article entitled “Soluble Tumor Necrosis Factor Receptor 1 Released by Skin-Derived Mesenchymal Stem Cells Is Critical for Inhibiting Th17 Cell Differentiation” revealed a novel mechanism of mesenchymal stem cells (MSCs)-mediated immune regulation. Stem cells, including embryonic stem cells and adult stem cells, are a class of cells with self-renewal and differentiation potential. MSCs are adult stem cells, derived from early developed mesoderm. MSCs have  multi-directional differentiation potential, i.e.  capacity to differentiate into not only mesoderm-derived cells such as adipocytes, osteocytes and chondrocytes, but also ectoderm or endoderm-derived cells such as hepatocytes, cardiocytes and neurons. The potential of MSCs provide important raw materials for the treatment of regenerative medicine. MSCs can also regulate  immune cells, including both innate and adaptive immune cells. In addition, MSCs are MHCII negative, which leads to low immunogenicity. Therefore MSCs can be directly used in clinical transplantation. These characteristics make MSCs an ideal seed cell for the treatment of autoimmune diseases. Th17 cells play an important role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Cytokines TGF-β1 and IL-6 can induce CD4⁺ naïve T cells to differentiate into Th17 cells in vitro, while it is still poorly understood whether other factors can control the differentiation of Th17 cells. MSCs secrete a variety of factors involved in immune regulation, while the factors affecting Th17 cell differentiation are still not clear. Under the supervision of Dr. Wang, Ke Fang et al. found that intraperitoneal injection of skin-derived MSCs (S-MSCs) could effectively alleviate the inflammatory phenotype of EAE. Activated S-MSCs expressed high levels of secreted tumor necrosis factor receptor-1(sTNFR1), while sTNFR1 could neutralize the biological activity of TNF-α. Further studies have found that TNF-α could promote the differentiation of Th17 cells, while the immunoregulatory capability of S-MSCs was impaired on the treatment of EAE with MSC intrinsic TNFR1 konck-down. In conclusion, this study showed that S-MSCs can neutralize TNF-α to inhibit the promotion of TNF-α on Th17 cell differentiation through the secretion of sTNFR1, which ultimately leads to the alleviation of EAE. The current findings reveal a novel mechanism of MSCs-mediated immunoregulatory function, which provides a new rationale for the clinical application of MSCs. The research was supported by Key Program of National Natural Science Foundation of China (No. 31330026), Training Program of the Major Research Plan of the National Natural Science Foundation of China (No. 91029730) and "973 projects" of Ministry of Science and Technology (No.2014CB541905; No.2012CB917100).