Mesenchymal stem cells alleviate inflammatory responses through regulation of T-cell subsets.

Immune-mediated inflammatory disease (IMID) is a complex disorder characterized by excessive immune responses involving T cells and their subsets, leading to direct tissue damage. T cells can be broadly categorized into CD4+ T cells and CD8+ T cells. CD4+ T cells are composed of several subsets, including T helper (Th)1, Th2, Th9, Th17, Th22, follicular helper T cells (Tfhs), and regulatory T cells (Tregs), while effector CD8+ T cells consist mainly of cytotoxic T cells (CTLs). Current therapies for IMID are ineffective, prompting exploration into mesenchymal stem cells (MSCs) as a promising clinical treatment due to their immunomodulatory effects and self-renewal potential. Recent studies have shown that MSCs can suppress T cells through direct cell-to-cell contact or secretion of soluble cytokines. Nevertheless, the precise effects of MSCs on T cell subsets remain inadequately defined. In this review, we summarize the most recent studies that have examined how MSCs modulate one or more effector T-cell subsets and the mechanisms behind these modifications in vitro and several mouse models of clinical inflammation. This also provides theoretical support and novel insights into the efficacy of clinical treatments involving MSCs. However, the efficacy of MSC therapies in clinical models of inflammation varies, showing effective remission in most cases, but also with exacerbation of T-cell-mediated inflammatory damage in some instances.

Acacetin antagonized lipotoxicity in pancreatic ß-cells via ameliorating oxidative stress and endoplasmic reticulum stress.

PURPOSE: During the pathogenesis and progression of diabetes, lipotoxicity is a major threat to the function and survival of pancreatic ß-cells. To battle against the lipotoxicity induced cellular damages, the present study investigated the beneficial effects of acacetin, a natural antioxidant, on free fatty acid (FFA) stressed RINm5F cells and the potential mechanism involved. MATERIALS AND METHODS: RINm5F cells with or without 1 h pretreatment of acacetin were treated with 0.35 mM sodium palmitate for 24 h. Cell viability, intracellular reactive oxygen species (ROS) level, antioxidant capacity, cellular apoptosis, and endoplasmic reticulum (ER) stress biomarker expression were investigated. RESULTS: Our experiments demonstrated that acacetin treatment significantly scavenged the intracellular ROS, upregulated the endogenous antioxidant enzymes, and diminished the sub-G1 DNA fraction in the cells exposed to FFA, suggesting its efficacy against oxidative stress. Meanwhile, acacetin treatment significantly mitigated the overload of intracellular Ca2+ and reduced the pro-apoptotic protein expression in the FFA stimulated cells, and thereby attenuated the ER stress-mediated cell apoptosis. Furthermore, siRNA interference results confirmed that the suppressing of C/EBP-homologous protein (CHOP) was critical to improve FFA-induced reduction in cell viability and ameliorated the ER stress caused by FFA stimulation. CONCLUSIONS: Acacetin may antagonize lipotoxicity in pancreatic cells by attenuating the oxidative stress and ER stress.