// Zhuoya Wang 1, * , Weiwei Wang 1, * , Yun Hou 2 , Aiping Zhang 1 , Guoyan Wang 3 , Junzhu Yi 1 , Qiang Fu 1 and Xiying Luan 1, 4 1 Department of Immunology, Binzhou Medical University, Shandong Province, Yantai 264003, People’s Republic of China 2 Department of Histology and Embryology, Binzhou Medical University, Shandong Province, Yantai 264003, People’s Republic of China 3 Department of Laboratory, Affiliated Yantai Hospital of Binzhou Medical University, Yantai 264100, People’s Republic of China 4 Taishan Scholar Immunology Program, Binzhou Medical University, Yantai, Shandong Province 264003, People’s Republic of China * Theses authors contributed equally to this work Correspondence to: Xiying Luan, email: xyluan@sohu.com Keywords: mesenchymal stromal cells (MSCs); IL-10 + T cells; experimental autoimmune encephalomyelitis (EAE); PDLs; IFN-γ Received: November 09, 2017 Accepted: January 02, 2018 Published: January 02, 2018 ABSTRACT Mesenchymal stromal cells (MSCs) are regarded as promising candidates for cell-based therapies in the treatment of autoimmune and inflammation-related diseases, such as multiple sclerosis (MS), due to their immunomodulatory capacity. High levels of inflammatory cytokines represent one of the salient characteristics of MS. Obviously, there is an interplay between MSCs and inflammatory cytokines after MSCs transplantation, which may be related to the therapeutic effects of MSCs. Here, we investigate the effects of IFN-γ and IL-1β on the generation of IL-10 + T cell subsets mediated by human placenta-derived mesenchymal stromal cells (hPMSCs) as evaluated both in vitro and in a mouse model of experimental autoimmune encephalomyelitis (EAE). Our results demonstrated that the percent of IL-10 + T cells induced by hPMSCs was enhanced by IFN-γ and IL-1β through an up-regulation in the expression of programmed death ligand 1 and 2 (PDLs) in hPMSCs in vitro . IFN-γ promoted the expression of PDLs via activation of IRF-1 triggered by the JAK/STAT signaling pathway. Both hPMSCs and IFN-γ-pretreated hPMSCs increased the percent of IL-10 + T cells in EAE mice and further alleviated EAE symptoms as compared with the PBS treatment. The percent of CD4 + IL-10 + T cells was further enhanced in EAE mice receiving IFN-γ-pretreated hPMSCs as compared with mice receiving hPMSCs alone. Taken together, IFN-γ and IL-1β enhance the immunoregulatory capacities of hPMSCs with regard to the generation of IL-10 + T cells and, in this way, enable amplify the therapeutic effects of hPMSCs upon autoimmune diseases, such as MS.