In Vitro Analysis of Immunomodulatory Effects of Mesenchymal Stem Cell- and Tumor Cell -Derived Exosomes on Recall Antigen-Specific Responses Publisher Pubmed



Fathollahi A¹ ; Hashemi SM^{1, 2} ; Haji Molla Hoseini M¹ ; Yeganeh F¹
Source: International Immunopharmacology Published:2019

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 (MOG 35–55 ) 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 (T H )1 and T H 2 responses. However, the IFN-γ level did not decrease. The expression of Rorc and Elf4, which are the activator and inhibitor for differentiation of T H 17 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. © 2018 Elsevier B.V.