Anwar Fathollahi1, Seyed Mahmoud Hashemi2, Mostafa Haji Molla Hoseini1, Farshid Yeganeh3. 1. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: fyeganeh@sbmu.ac.ir.
Abstract
BACKGROUND: The aim of the present study was to evaluate in vitro effects of exosomes derived from mesenchymal stem cells (MSCs) or tumor cells on recall-antigen-specific immune responses. METHODS: The exosomes were isolated from the supernatant of the cultures of the adipose-derived MSCs, and 4T1 cell line. The splenocytes isolated from experimental autoimmune encephalomyelitis (EAE) mice were utilized to evaluate the effects of exosomes on recall-antigen-specific responses. The expression of master regulators for T cell sub-types and the levels of their corresponding cytokines were evaluated. RESULTS: Treatment by disease-inducing peptide (MOG35-55) combined with MSC-EXO or by MOG+TEX enhanced the expression of Foxp3 as the master regulator for Treg cells; by comparing with splenocytes which were treated by MOG. Nonetheless, the production of IL-10 and TGF-β were increased only in splenocytes treated by MOG+TEX. Additionally, treatments of splenocytes by MOG+TEX and MOG+MSC-EXO decreased the expression of Tbx21 and Gata3, as the master regulator for T helper (TH)1 and TH2 responses. However, the IFN-γ level did not decrease. The expression of Rorc and Elf4, which are the activator and inhibitor for differentiation of TH17 respectively were increased after splenocytes was treated by MOG+TEX. However, a reduction in Rorc and Elf4 levels was observed when splenocytes were treated by MOG+MSC-EXO. Indeed, the concentration of IL-17 did not alter significantly following the treatment by MOG+exosomes. CONCLUSION: It was ultimately attained that TEX and MSC-EXO utilized various mechanisms to modulate the recall immune responses. TEX was more potent than MSC-EXO to induce regulatory responses by upregulating the production of Foxp3, IL-10, and TGF-β.
BACKGROUND: The aim of the present study was to evaluate in vitro effects of exosomes derived from mesenchymal stem cells (MSCs) or tumor cells on recall-antigen-specific immune responses. METHODS: The exosomes were isolated from the supernatant of the cultures of the adipose-derived MSCs, and 4T1 cell line. The splenocytes isolated from experimental autoimmune encephalomyelitis (EAE) mice were utilized to evaluate the effects of exosomes on recall-antigen-specific responses. The expression of master regulators for T cell sub-types and the levels of their corresponding cytokines were evaluated. RESULTS: Treatment by disease-inducing peptide (MOG35-55) combined with MSC-EXO or by MOG+TEX enhanced the expression of Foxp3 as the master regulator for Treg cells; by comparing with splenocytes which were treated by MOG. Nonetheless, the production of IL-10 and TGF-β were increased only in splenocytes treated by MOG+TEX. Additionally, treatments of splenocytes by MOG+TEX and MOG+MSC-EXO decreased the expression of Tbx21 and Gata3, as the master regulator for T helper (TH)1 and TH2 responses. However, the IFN-γ level did not decrease. The expression of Rorc and Elf4, which are the activator and inhibitor for differentiation of TH17 respectively were increased after splenocytes was treated by MOG+TEX. However, a reduction in Rorc and Elf4 levels was observed when splenocytes were treated by MOG+MSC-EXO. Indeed, the concentration of IL-17 did not alter significantly following the treatment by MOG+exosomes. CONCLUSION: It was ultimately attained that TEX and MSC-EXO utilized various mechanisms to modulate the recall immune responses. TEX was more potent than MSC-EXO to induce regulatory responses by upregulating the production of Foxp3, IL-10, and TGF-β.