Single-Cell Analysis Uncovers Striking Cellular Heterogeneity of Lung-Infiltrating Regulatory T Cells during Eosinophilic versus Neutrophilic Allergic Airway Inflammation.

Allergic airway inflammation results from uncontrolled immune responses to environmental Ags. Although it is well established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types such as eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the mechanisms responsible for such pathogenesis remain elusive. Foxp3+ regulatory T cells (Tregs) are essential immune regulators during chronic inflammation, including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display heterogeneity and tissue residency. Whether diverse allergic airway inflammatory responses influence infiltrating Treg heterogeneity or Treg lung residency has not been explored. We employed an unbiased single-cell RNA sequencing approach to investigate lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation. We found that lung-infiltrating Tregs are highly heterogeneous, and that Tregs displaying lung-resident phenotypes are significantly different depending on the types of inflammation. Treg expression of ST2, a receptor for alarmin IL-33, was predominantly associated with eosinophilic inflammation and tissue residency. Nevertheless, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation or the generation of lung-resident Tregs. These results uncover a stark heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results indicate that varying types of inflammation may give rise to phenotypically distinct lung-resident Tregs, underscoring a (to our knowledge) novel mechanism by which inflammatory cues may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms.

Hydrogen production in microbial electrolysis cells with biocathodes.

Electroautotrophic microbes at biocathodes in microbial electrolysis cells (MECs) can catalyze the hydrogen evolution reaction with low energy demand, facilitating long-term stable performance through specific and renewable biocatalysts. However, MECs have not yet reached commercialization due to a lack of understanding of the optimal microbial strains and reactor configurations for achieving high performance. Here, we critically analyze the criteria for the inocula selection, with a focus on the effect of hydrogenase activity and microbe-electrode interactions. We also evaluate the impact of the reactor design and key parameters, such as membrane type, composition, and electrode surface area on internal resistance, mass transport, and pH imbalances within MECs. This analysis paves the way for advancements that could propel biocathode-assisted MECs toward scalable hydrogen gas production.

Integrated dark-fermentation-microbial electrosynthesis for efficient wastewater treatment and bioenergy recovery.

High ammonia concentration in wastewater can hinder methane production rate in anaerobic digestion (AD)-microbial electrosynthesis systems (ADMES). To address this issue, a dual-chamber reactor was fabricated using an anion exchange membrane (AEM) to separate the dark-fermentation (DF) and ADMES process, preventing ammonia migration from the DF chamber to the ADMES chamber. As a result, the DF-ADMES achieved a high methane yield based on chemical oxygen demand (COD) of 0.35 L CH4/gCOD compared to control operation AD (0.23 L CH4/gCOD) and ADMES (0.30 L CH4/gCOD). Additionally, hydrogen could be recovered from the DF chamber which improved the energy efficiency of the DF-ADMES reactor (91.7 %) as compared to control AD (53.4 %) and ADMES (71.9 %). Thus, a dual-chamber DF-ADMES with an AEM separator could be a feasible design for scalable treatment of high nitrogen-containing wastewater and high bioenergy recovery.

Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice.

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling.

Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.

The normal stress response in humans is governed by the hypothalamic-pituitary-adrenal (HPA) axis through heightened mechanisms during stress, raising blood levels of the glucocorticoid hormone cortisol. Glucocorticoids are quintessential compounds that balance the proper functioning of numerous systems in the mammalian body. They are also generated synthetically and are the preeminent therapy for inflammatory diseases. They act by binding to the nuclear receptor transcription factor glucocorticoid receptor (GR), which has two main isoforms (GRα and GRß). Our classical understanding of glucocorticoid signaling is from the GRα isoform, which binds the hormone, whereas GRß has no known ligands. With glucocorticoids being involved in many physiological and cellular processes, even small disruptions in their release via the HPA axis, or changes in GR isoform expression, can have dire ramifications on health. Long-term chronic glucocorticoid therapy can lead to a glucocorticoid-resistant state, and we deliberate how this impacts disease treatment. Chronic glucocorticoid treatment can lead to noticeable side effects such as weight gain, adiposity, diabetes, and others that we discuss in detail. There are sexually dimorphic responses to glucocorticoids, and women tend to have a more hyperresponsive HPA axis than men. This review summarizes our understanding of glucocorticoids and critically analyzes the GR isoforms and their beneficial and deleterious mechanisms and the sexual differences that cause a dichotomy in responses. We also discuss the future of glucocorticoid therapy and propose a new concept of dual GR isoform agonist and postulate why activating both isoforms may prevent glucocorticoid resistance.

Copper foam supported g-C3N4-metal-organic framework bacteria biohybrid cathode catalyst for CO2 reduction in microbial electrosynthesis.

Microbial electrosynthesis (MES) presents a versatile approach for efficiently converting carbon dioxide (CO2) into valuable products. However, poor electron uptake by the microorganisms from the cathode severely limits the performance of MES. In this study, a graphitic carbon nitride (g-C3N4)-metal-organic framework (MOF) i.e. HKUST-1 composite was newly designed and synthesized as the cathode catalyst for MES operations. The physiochemical analysis such as X-ray diffraction, scanning electron microscopy (SEM), and X-ray fluorescence spectroscopy showed the successful synthesis of g-C3N4-HKUST-1, whereas electrochemical assessments revealed its enhanced kinetics for redox reactions. The g-C3N4-HKUST-1 composite displayed excellent biocompatibility to develop electroactive biohybrid catalyst for CO2 reduction. The MES with g-C3N4-HKUST-1 biohybrid demonstrated an excellent current uptake of 1.7 mA/cm2, which was noted higher as compared to the MES using g-C3N4 biohybrid (1.1 mA/cm2). Both the MESs could convert CO2 into acetic and isobutyric acid with a significantly higher yield of 0.46 g/L.d and 0.14 g/L.d respectively in MES with g-C3N4-HKUST-1 biohybrid and 0.27 g/L.d and 0.06 g/L.d, respectively in MES with g-C3N4 biohybrid. The findings of this study suggest that g-C3N4-HKUST-1 is a highly efficient catalytic material for biocathodes in MESs to significantly enhance the CO2 conversion.