Mucosal associated invariant T cells are differentially impaired in tolerant and immunosuppressed liver transplant recipients

Mucosal associated invariant T (MAIT-) cells represent a semi-invariant T cell population responsive to microbial vitamin B metabolite and innate cytokine stimulation, executing border tissue protection and particularly contributing to human liver immunity. The impact of immunosuppressants on MAIT cell biology alone and in context with solid organ transplantation has not been thoroughly examined. Here, we demonstrate that in vitro cytokine activation of peripheral MAIT cells from healthy individuals was impaired by glucocorticoids, whereas antigen-specific stimulation was additionally sensitive to calcineurin inhibitors. In liver transplant (LTx) recipients, significant depletion of peripheral MAIT cells was observed that was largely independent of the type and dosage of immunosuppression, equally applied to tolerant patients, and was reproducible in kidney transplant recipients. However, MAIT cells from tolerant LTx patients exhibited a markedly diminished ex vivo activation signature, associated with individual regain of functional competence toward antigenic and cytokine stimulation. Still, MAIT cells from tolerant and treated liver recipients exhibited high levels of PD1, accompanied by functional impairment particularly toward bacterial stimulation that also affected polyfunctionality. Our data suggest interlinked effects of primary liver pathology and immunosuppressive treatment on overall MAIT cell fitness after transplantation and propose their monitoring in context with tolerance induction protocols

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Metal Loading Effect on the Activity of Co 3 O 4 /N-Doped Reduced Graphene Oxide Nanocomposites as Bifunctional Oxygen Reduction/Evolution Catalysts

International audienceThe development of effective and stable reversible oxygen electrodes is of upmost importance for bringing regenerative energy storage and conversion systems to a commercial reality. However, realization of such electrodes is motivated by low activity and instability of the current electrocatalysts working for both water splitting and oxygen reduction. Herein, we report a series of Co3O4/graphene-based catalysts with different Co mass loadings prepared by using a facile one-step hydrothermal route. N-doped reduced graphene oxide (NRGO) was utilized as a substrate for the deposition of oxide particles. The structural properties and surface composition of the different materials were investigated by powder X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy measurements. The effect of Co mass loading on the morphostructural properties of oxide nanoparticles and also on their electroactivity towards the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) was addressed. This study revealed the optimum range for metal loading on the graphene substrate. Co3O4/NRGO with a Co mass loading of 30 wt.% exhibits the highest activity towards ORR and OER, with a reversibility criterion of 763 mV. This work is very helpful for the electrocatalysis community, and will allow effective catalysts to be developed for high-power metal/air battery or regenerative fuel cell systems, based on earth-abundant and scalable electro-catalysts