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Inducing donor-specific immunological tolerance, which avoids the complications of long-term immunosuppression, is an important goal in organ transplantation. Interleukin-35 (IL-35), a cytokine identified in 2007, is mainly secreted by regulatory T cells (Tregs) and is essential for Tregs to exert their maximal immunoregulatory activity in vitro and in vivo. A growing number of studies show that IL-35 plays an important role in autoimmune diseases and infectious diseases. Recent research has shown that IL-35 could effectively alleviate allograft rejection and has the potential to be a novel therapeutic strategy for graft rejection. With increasing study of immunoregulation, cell-based therapy has become a novel approach to attenuate rejection after transplantation. Mesenchymal stem cells (MSCs), which exhibit important properties of multilineage differentiation, tissue repair, and immunoregulation, have recently emerged as attractive candidates for cell-based therapeutics, especially in transplantation. Accumulating evidence demonstrates that the therapeutic abilities of MSCs can be amplified by gene modification. Therefore, researchers have constructed IL-35 gene-modified MSCs and explored their functions and mechanisms in some disease models. In this review, we discuss the potential tolerance-inducing effects of MSCs in transplantation and briefly introduce the immunoregulatory functions of the IL-35 gene-modified MSCs. [ABSTRACT FROM AUTHOR]

Exosomes have been intensively studied in autoimmune diseases, and circulating exosomes and microvesicles have also been explored in autoimmune thyroiditis (AITD). However, the role of thyroid cell-derived exosomes in immune responses is unclear. We showed that IFN-γ-treated Nthy-ori 3-1 cell-derived exosomes (IFN-γ-Exo) harbored TPO, HSP60 and MHC-II and activated dendritic cells (DCs) in vitro. Compared with Exo-targeted DCs (DC Exo), IFN-γ-Exo-targeted DCs (DC IFN-γ-Exo) promoted the expression and release of proinflammatory cytokines, such as IFN-γ, IL-17A and IL-22, from CD4+ T lymphocytes and inhibited the expression and release of anti-inflammatory cytokines, such as IL-4, IL-10 and TGF-β1; however, IFN-γ-Exo did not have this effect compared with Nthy-ori 3-1 cell-derived exosomes (Exo). DC IFN-γ-Exo stimulates the expression and release of cytokines from CD4+ T lymphocytes more efficiently than IFN-γ-Exo. Thus, DC IFN-γ-Exo may effectively induce CD4+ T lymphocyte-mediated immune responses and play a role in the occurrence and development of AITD. • IFN-γ-treated thyroid cell-derived exosomes (IFN-γ-Exo) express TPO, HSP60, MHC-II. • IFN-γ-Exo activate dendritic cells (DCs). • IFN-γ-Exo need to activate DCs before triggering CD4+ T lymphocyte differentiation. [ABSTRACT FROM AUTHOR]