Establishment of iPSC-Derived MSCs Expressing hsa-miR-4662a-5p for Enhanced Immune Modulation in Graft-Versus-Host Disease (GVHD).

The immune-modulatory effects of mesenchymal stromal cells (MSCs) are widely used to treat inflammatory disorders, with indoleamine 2,4-dioxygenase-1 (IDO-1) playing a pivotal role in suppressing stimulated T-cell proliferation. Taking that three-dimensional (3D) cultures enhance MSCs' anti-inflammatory properties compared with two-dimensional (2D) cultures, the differentially expressed miRNAs were examined. Thus, we identified hsa-miR-4662a-5p (miR-4662a) as a key inducer of IDO-1 via its suppression of bridging integrator-1 (BIN-1), a negative regulator of the IDO-1 gene.

Chemical Coaxing of Mesenchymal Stromal Cells by Drug Repositioning for Nestin Induction.

Mesenchymal stromal cells (MSCs) display heterogeneity in origin and functional role in tissue homeostasis. Subsets of MSCs derived from the neural crest express nestin and serve as niches in bone marrow, but the possibility of coaxing MSCs into nestin-expresing cells for enhanced supportive activity is unclear. In this study, as an approach to the chemical coaxing of MSC functions, we screened libraries of clinically approved chemicals to identify compounds capable of inducing nestin expression in MSCs.

IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway.

Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients.

Lyophilizable and Multifaceted Toll-like Receptor 7/8 Agonist-Loaded Nanoemulsion for the Reprogramming of Tumor Microenvironments and Enhanced Cancer Immunotherapy.

The low therapeutic efficacy of current cancer immunotherapy is related to nonimmunogenic and immunosuppressive tumor microenvironments (TMEs). To overcome these limitations, both the immune priming of antitumoral lymphocytes and the reprogramming of immunosuppressive factors in TMEs are essential. Here, we suggest a nanoemulsion (NE)-based immunotherapeutic platform that can not only modulate tumor-induced suppression but also induce an effective cell-mediated immune response for T cell proliferation.

Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation.

Natural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells.

Liver Antioxidant Enzyme Activities Increase After Taurine in Ovariectomized Rats.

The present study was performed to know the effects of taurine on the lipid level of plasma and liver, lipid peroxidation and antioxidative enzyme activities of liver tissue in ovariectomized (OVX) rats fed cholesterol. Twenty-four female SD rats (200 ± 5 g) were grouped; sham and ovariectomy groups, which were each randomly subgrouped; fed control and control supplemented with taurine (20 g/kg diet). The serum total cholesterol, TG (triglyceride), LDL-cholesterol, athrogenic index, and HDL-cholesterol of taurine diet group were not statistically different.

An increased level of IL-6 suppresses NK cell activity in peritoneal fluid of patients with endometriosis via regulation of SHP-2 expression.

Study Question: Is the decreased natural killer (NK) cell cytolytic activity in the peritoneal fluid (PF) of endometriosis patients due to primary cytokine activity?

Summary Answer: An increased level of interleukin-6 (IL-6) in the PF of patients with endometriosis suppresses NK cell cytolytic activity by down-regulating cytolytic granule components, such as granzyme B and perforin, through the modulation of Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) expression.

What Is Already Known: Endometriosis is known to be related to a defect in NK cell cytolytic activity. Additionally, the levels of inflammatory cytokines are elevated in the PF of women with endometriosis.

Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stem cells.

Bone morphogenetic proteins (BMPs) that belong to the transforming growth factor-β (TGF-β) superfamily cytokines, play crucial roles in hematopoiesis. However, roles of Smad6 in hematopoiesis remained unknown in contrast to the other inhibitory Smad (I-Smad), Smad7. Here we show that Smad6 inhibits erythropoiesis in human CD34(+) cord blood hematopoietic stem cells (HSCs).

Identification of a stroma-mediated Wnt/beta-catenin signal promoting self-renewal of hematopoietic stem cells in the stem cell niche.

With contrasting observations on the effects of beta-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt/beta-catenin signals on HSC regulation remains unclear. Here, we show a distinct mode of Wnt/beta-catenin signal that can regulate HSCs in a stroma-dependent manner. Stabilization of beta-catenin in the bone marrow stromal cells promoted maintenance and self-renewal of HSCs in a contact-dependent manner, whereas direct stabilization in hematopoietic cells caused loss of HSCs.

A novel function of interleukin-10 promoting self-renewal of hematopoietic stem cells.

Self-renewal of hematopoietic stem cells (HSCs) is key to their reconstituting ability, but the factors regulating the process remain poorly understood. Here, we show that Interleukin-10 (IL-10), a pleiotropic immune modulating cytokine, can also play a role in regulating HSC self-renewal. First, a quantitative decrease of primitive hematopoietic cell populations, but not more matured cells, was observed in the bone marrows of IL-10 disrupted mice as determined by long-term in vitro cultures or in vivo competitive repopulation assays.

Unique effects of Stat3 on the early phase of hematopoietic stem cell regeneration.

Self-renewal of hematopoietic stem cells (HSCs) is key to their reconstituting ability, but the signaling pathways that regulate this process remain poorly understood. Here we show that transduction of adult mouse bone marrow cells with a constitutively activated form of Stat3 (Stat3-C) increased their regenerative activity in lethally irradiated recipients. Conversely, transduction of these cells with a dominant-negative form of Stat3 suppressed their regenerative activity.