While human Tregs hold immense promise for immunotherapy, their biologic variability poses challenges for clinical use. Here, we examined clinically-relevant activities of defined subsets of freshly-isolated and culture-expanded human PBMC-derived Tregs. Unlike highly suppressive but plastic memory Tregs (memTreg), naïve Tregs (nvTreg) exhibited the greatest proliferation, suppressive capacity after stimulation, and Treg lineage fidelity. Yet, unlike memTregs, nvTregs lack Fucosyltransferase VII and display low sLeX expression, with concomitant poor homing capacity. In vitro nvTreg expansion augmented their suppressive function, but did not alter the nvTreg sLeX-l ° w glycome. However, exofucosylation of the nvTreg surface yielded high sLeX expression, promoting endothelial adhesion and enhanced inhibition of xenogeneic aGVHD. These data indicate that the immature Treg glycome is under unique regulation and that adult PBMCs can be an ideal source of autologous-derived therapeutic Tregs, provided that subset selection and glycan engineering are engaged to optimize both their immunomodulation and tropism for inflammatory sites.

IntroductionOvarian cancer is one of the most fatal malignancies of the female reproductive system. The purpose of this study is to explore the mechanism of Actin Related Protein 2/3 Complex Subunit 1B(ARPC1B) in the progression of ovarian cancer.MethodsThe expressions and prognostic value of ARPC1B in ovarian cancer were identified using the GEPIA database and the Kaplan-Meier Plotter database. The expression of ARPC1B was manipulated to evaluate its impact on the malignant phenotypes of ovarian cancer. The cell proliferation ability was analyzed through CCK-8 assay and clone formation assay. The cell migration and invasion capacity was evaluated through wound healing assay and trans well assay. Mice xenografts were conducted to measure the effects of ARPC1B on tumor development in vivo.ResultsOur data suggested that ARPC1B was overexpressed in ovarian cancer, which was correlated with a poorer survival compared to low mRNA expression of ARPC1B in ovarian cancer patients. The overexpression of ARPC1B promoted cell proliferation, migration, and invasion of ovarian cancer cells. Conversely, the knockdown of ARPC1B resulted in the opposite effect. Additionally, ARPC1B expression could activate Wnt/β-catenin signaling pathway. The administration of the β-catenin inhibitor XAV-939 abolished the promotion of cell proliferation, migration, and invasion activities induced by ARPC1B overexpression in vitro.ConclusionsARPC1B was overexpressed in ovarian cancer and was correlated with poor prognosis. ARPC1B promoted ovarian cancer progression through activation of Wnt/β-catenin Signaling Pathway.

The purpose of this study was to examine whether myeloid dendritic cells (mDCs) from patients with multiple sclerosis (MS) and healthy controls (HCs) become similarly tolerogenic when exposed to IL-27 as this may represent a potential mechanism of autoimmune dysregulation. Our study focused on natural mDCs that were isolated from HCs and MS patient peripheral blood mononuclear cells (PBMCs). After a 24-h treatment with IL-27 ± lipopolysaccharide (LPS), the mDCs were either harvested to identify IL-27-regulated gene expression or co-cultured with naive T-cells to measure how the treated DC affected T-cell proliferation and cytokine secretion. mDCs isolated from HCs but not untreated MS patients became functionally tolerogenic after IL-27 treatment. Although IL-27 induced both HC and untreated MS mDCs to produce similar amounts of IL-10, the tolerogenic HC mDCs expressed PD-L2, IDO1, and SOCS1, while the non-tolerogenic untreated MS mDCs expressed IDO1 and IL-6R. Cytokine and RNA analyses identified two signature blocks: the first identified genes associated with mDC tolerizing responses to IL-27, while the second was associated with the presence of MS. In contrast to mDCs from untreated MS patients, mDCs from HCs and IFNb-treated MS patients became tolerogenic in response to IL-27. The genes differentially expressed in the different donor IL-27-treated mDCs may contain targets that regulate mDC tolerogenic responses.