IL-6 enhances CD4 cell motility by sustaining mitochondrial Ca2+ through the noncanonical STAT3 pathway

Interleukin 6 (IL-6) is known to regulate the CD4 T cell function by inducing gene expression of a number of cytokines through activation of Stat3 transcription factor. Here, we reveal that IL-6 strengthens the mechanics of CD4 T cells. The presence of IL-6 during activation of mouse and human CD4 T cells enhances their motility (random walk and exploratory spread), resulting in an increase in travel distance and higher velocity. This is an intrinsic effect of IL-6 on CD4 T-cell fitness that involves an increase in mitochondrial Ca2+. Although Stat3 transcriptional activity is dispensable for this process, IL-6 uses mitochondrial Stat3 to enhance mitochondrial Ca2+-mediated motility of CD4 T cells. Thus, through a noncanonical pathway, IL-6 can improve competitive fitness of CD4 T cells by facilitating cell motility. These results could lead to alternative therapeutic strategies for inflammatory diseases in which IL-6 plays a pathogenic role.

PVA Films with Mixed Silver Nanoparticles and Gold Nanostars for Intrinsic and Photothermal Antibacterial Action

PVA films with embedded either silver nanoparticles (AgNP), NIR-absorbing photothermal gold nanostars (GNS), or mixed AgNP+GNS were prepared in this research. The optimal conditions to obtain stable AgNP+GNS films with intact, long lasting photothermal GNS were obtained. These require coating of GNS with a thiolated polyethylene glycol (PEG) terminated with a carboxylic acid function, acting as reticulant in the film formation. In the mixed AgNP+GNS films, the total noble metal content is <0.15% w/w and in the Ag films < 0.025% w/w. The slow but prolonged Ag+ release from film-embedded AgNP (8–11% of total Ag released after 24 h, in the mixed films) results in a very strong microbicidal effect against planktonic Escherichia coli and Staphylococcus aureus bacterial strains (the release of Au from films is instead negligible). Beside this intrinsic effect, the mixed films also exert an on-demand, fast hyperthermal bactericidal action, switched on by NIR laser irradiation (800 nm, i.e., inside the biotransparent window) of the localized surface plasmon resonance (LSPR) absorption bands of GNS. Temperature increases of 30 °C are obtained using irradiances as low as 0.27 W/cm2. Moreover, 80–90% death on both strains was observed in bacteria in contact with the GNS-containing films, after 30 min of irradiation. Finally, the biocompatibility of all films was verified on human fibroblasts, finding negligible viability decrease in all cases.

Intrinsic effect of interfacial coupling on the high-frequency intralayer modes in twisted multilayer MoTe2

The interfacial coupling at the interface makes van der Waals heterostructures (vdWHs) exhibit many unique properties that cannot be realized in its constituents. Such study usually starts with a twist...

The intrinsic effect of co-feeding water on the formation of active/deactivating species in the methanol-to-hydrocarbons reaction on ZSM-5 zeolite

Water is formed and added in the conversion of methanol to hydrocarbons, slowing down both the reaction and deactivation rates. The retained species that are reaction intermediates and coke precursors are swept/desorbed, particularly those on silanol sites.

Food Timing, Circadian Rhythm and Chrononutrition: A Systematic Review of Time-Restricted Eating’s Effects on Human Health

Introduction: Recent observations have shown that lengthening the daily eating period may contribute to the onset of chronic diseases. Time-restricted eating (TRE) is a diet that especially limits this daily food window. It could represent a dietary approach that is likely to improve health markers. The aim of this study was to review how time-restricted eating affects human health. Method: Five general databases and six nutrition journals were screened to identify all studies published between January 2014 and September 2020 evaluating the effects of TRE on human populations. Results: Among 494 articles collected, 23 were finally included for analysis. The overall adherence rate to TRE was 80%, with a 20% unintentional reduction in caloric intake. TRE induced an average weight loss of 3% and a loss of fat mass. This fat loss was also observed without any caloric restriction. Interestingly, TRE produced beneficial metabolic effects independently of weight loss, suggesting an intrinsic effect based on the realignment of feeding and the circadian clock. Conclusions: TRE is a simple and well-tolerated diet that generates many beneficial health effects based on chrononutrition principles. More rigorous studies are needed, however, to confirm those effects, to understand their mechanisms and to assess their applicability to human health.

TLR9-deficiency in B cells Promotes Immune Tolerance via IL-10 in a Type 1 Diabetes Mouse Model

Toll-like receptor 9 (TLR9) is highly expressed in B cells and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on beta cell autoimmunity is not known. To fill this knowledge gap, we generated non-obese diabetic (NOD) mice with a B cell-specific deficiency of TLR9 (TLR9^fl/fl/CD19-Cre+ NOD). The B cell-specific deletion of TLR9 resulted in near complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of IL-10-producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune-stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10-producing B cells. Molecular analysis revealed a network of TLR9 with MMPs, TIMP1 and CD40, all of which are inter-connected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immuno-pathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.

TLR9-deficiency in B cells Promotes Immune Tolerance via IL-10 in a Type 1 Diabetes Mouse Model

Toll-like receptor 9 (TLR9) is highly expressed in B cells and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on beta cell autoimmunity is not known. To fill this knowledge gap, we generated non-obese diabetic (NOD) mice with a B cell-specific deficiency of TLR9 (TLR9^fl/fl/CD19-Cre+ NOD). The B cell-specific deletion of TLR9 resulted in near complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of IL-10-producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune-stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10-producing B cells. Molecular analysis revealed a network of TLR9 with MMPs, TIMP1 and CD40, all of which are inter-connected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immuno-pathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.