MicroRNA-146a regulates ICOS–ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres

Tight control of T follicular helper (Tfh) cells is required for optimal maturation of the germinal centre (GC) response. The molecular mechanisms controlling Tfh-cell differentiation remain incompletely understood. Here we show that microRNA-146a (miR-146a) is highly expressed in Tfh cells and peak miR-146a expression marks the decline of the Tfh response after immunization. Loss of miR-146a causes cell-intrinsic accumulation of Tfh and GC B cells. MiR-146a represses several Tfh-cell-expressed messenger RNAs, and of these, ICOS is the most strongly cell autonomously upregulated target in miR-146a-deficient T cells. In addition, miR-146a deficiency leads to increased ICOSL expression on GC B cells and antigen-presenting cells. Partial blockade of ICOS signalling, either by injections of low dose of ICOSL blocking antibody or by halving the gene dose of Icos in miR-146a-deficient T cells, prevents the Tfh and GC B-cell accumulation. Collectively, miR-146a emerges as a post-transcriptional brake to limit Tfh cells and GC responses.This work was funded by the National Health and Medical Research Council (NHMRC) program and project grants and Elizabeth Blackburn Fellowship to C.G.V., International Postgraduate Research Scholarship to A.P., NHMRC/MSRA Betty Cuthbert Fellowship to M.A.J., National Research Service Award F30HL110691 and UCLA/Caltech Medical Scientist Training Program to J.L.Z

Comparative Examination of Phytonutrients and Antioxidant Activity of Commonly Consumed Nuts and Seeds Grown in Vietnam

The aim of the present study was to determine the phenolics, carotenoids, B-vitamins, and antioxidant activity of nuts and seeds grown in Vietnam. The concentrations of carotenoids and B-vitamins may vary among the nuts and seeds. Watermelon seed contained the highest level of lutein while pumpkin seed was the β-carotene richest sample. Sachi inchi and sunflower seed comprised considerable levels of vitamin B1, B6, and B9. The phenolic analysis revealed that cashew contained the highest total amount of flavonoids (466.04 μg/g), with catechin, epicatechin, and procyanidin B2 predominating over the other flavonoids. Likewise, chlorogenic and neochlorogenic acids made up the highest total amount of phenolic acids in sunflower seed (1870.41 μg/g). Walnut appeared to possess the highest antioxidant activity evaluated by DPPH, ABTS, FRAP, and reducing power assays. The correlation analysis indicated strong positive correlations between total phenolic content with DPPH and FRAP values. Principal component analysis graphically showed the distant positioning of cashew and sunflower seed, highlighting their significantly higher levels of phenolics. The findings of the study would be useful to improve nutrient database contents for flavonoids and phenolic acids as well as to promote the consumption of nut and seed products in Vietnam

MicroRNA-146a regulates ICOS–ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres

Tight control of T follicular helper (Tfh) cells is required for optimal maturation of the germinal centre (GC) response. The molecular mechanisms controlling Tfh-cell differentiation remain incompletely understood. Here we show that microRNA-146a (miR-146a) is highly expressed in Tfh cells and peak miR-146a expression marks the decline of the Tfh response after immunization. Loss of miR-146a causes cell-intrinsic accumulation of Tfh and GC B cells. MiR-146a represses several Tfh-cell-expressed messenger RNAs, and of these, ICOS is the most strongly cell autonomously upregulated target in miR-146a-deficient T cells. In ddition,miR-146a deficiency leads to increased ICOSL expression on GC B cells and antigenpresentingcells. Partial blockade of ICOS signalling, either by injections of low dose of ICOSL blocking antibody or by halving the gene dose of Icos in miR-146a-deficient T cells, prevents the Tfh and GC B-cell accumulation. Collectively, miR-146a emerges as a post-transcriptional brake to limit Tfh cells and GC responses