In vitro analysis of immunomodulatory effects of mesenchymal stem cell- and tumor cell -derived exosomes on recall antigen-specific responses

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_H2 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_H17 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.