The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis

Abstract

SummaryMesenchymal stem cells (MSCs) are being explored extensively as a promising treatment for autoimmune diseases. We have recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we examined further the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on T helper type 1 (Th1) and Th17 cells and how long the inhibitory effect lasted, in order to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs decreased the production of Th1 and Th17 cytokines significantly, while the production of Th2 and regulatory T cell (Treg) cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-b] was elevated during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humour (AqH) were reduced in MSC-treated rats. Moreover, the ratio of Th17/Treg cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can regulate negatively both Th1 and Th17 responses and restore the balance of Th17/Tregs in the whole course of EAU, which is important for the regression of the disease.

Gene delivery with IFN-γ-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis

“…They prove that MSCs suppress the survival as well as the proliferation of T cells partially by increasing the proportion of regulatory T cells in vitro [33]. What is more, MSCs can negatively regulate both Th1 and Th17 responses and restore the balance of Th17/ Tregs in experimental autoimmune uveoretinitis [34]. Here, our results demonstrate that IFN-c-MSCs increase the proportion of CD4 ?…”

Multimodal Delivery of Isogenic Mesenchymal Stem Cells Yields Synergistic Protection from Retinal Degeneration and Vision Loss

“…MSC IV ‐secreted peptides have been shown to decrease circulating inflammatory cell numbers and inflammatory responses from circulating lymphocytes , macrophages , and dendritic cells . MSC influence on regulatory T cells was suggested as the mechanism by which MSCs promote allograft tolerance and ameliorate autoimmune uveoretinitis . Immune cell regulation is consistent with the role of MSCs and their progeny, which comprise stromal elements of endosteal and sinusoidal niches that support hematopoiesis in vivo and ectopic HSC niche formation de novo , .…”

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

“…Abundant information has been published on the relationship between MSC 2 and resolution of the inflammatory setting, and tissue protection and repair[24-34]. Some of the well-known anti-inflammatory effects mediated by MSC 2 are skewing macrophages to the M2 immunosuppressive alternative phenotype[35-41], promoting T cells to T regulatory (T reg ) cell differentiation[42-48], skewing monocyte-derived dendritic cells to a regulatory phenotype[49-54], inhibiting neutrophil influx and respiratory burst while maintaining or even increasing its phagocytic capacity[55-59], inhibiting mast cell degranulation[60-62], and inhibiting pro-inflammatory activities of T cells[63-72], natural killer (NK) cells[73-79] and B cells[80-84]. Furthermore, throughout the numerous reports describing the regulatory role of MSCs attenuating (at some point) inflammation, several intercellular molecular signals have consistently emerged as relevant.…”