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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that mainly affects women in their reproductive years. A complex interaction of environmental and genetic factors leads to the disruption of immune tolerance towards self, causing overt immune activation and production of autoantibodies that attack multiple organs. Kidney damage, termed lupus nephritis, is the leading cause of SLE-related morbidity and mortality. Autoantibodies are central to propagating lupus nephritis through forming immune complexes and triggering complements. Immunoglobulin G (IgG) potently activates complement; therefore, autoantibodies were mainly considered to be of the IgG isotype. However, studies revealed that over 50% of patients produce autoantibodies of the IgE isotype. IgE autoantibodies actively participate in disease pathogenesis as omalizumab treatment, a humanized anti-IgE monoclonal antibody, improved disease severity in an SLE clinical trial. IgE is a hallmark of T helper 2-associated immunity. Thus, T helper 2-associated immunity seems to play a pathogenic role in a subset of SLE patients. This review summarizes human and animal studies that illustrate type 2 immune responses involved during the pathology of SLE.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by alterations in social, repetitive, and anxiety-like behaviors. While emerging evidence suggest a gut-brain etiology in ASD, the underlying mechanisms remain unclear. To dissect this axis, we developed a germ-free BTBR mouse model for ASD. The absence of gut microbiota in male mice ameliorates ASD-associated behaviors and reduces populations of inflammatory brain-resident T cells. Additionally, CD4 + T cell depletion mitigates neuroinflammation and ASD behaviors, suggesting a gut-immune-brain axis. We identify several microbial and metabolic regulators of ASD, particularly those relevant to the glutamate/GABA ratio and 3-hydroxyglutaric acid. Using an in silico metabolite prediction model, we propose Limosilactobacillus reuteri IMB015 (IMB015) to be a probiotic candidate. Administration of IMB015 reduces the glutamate/GABA ratio and neuroinflammation, resulting in improved behaviors. Here we report a gut-immune-brain axis in which the gut microbiota and its metabolites can modulate brain-resident immune cells and ASD-associated behaviors. Using a germ-free BTBR mouse model of ASD-like behaviors, here the researchers demonstrated that the absence of gut microbiota significantly reduced social deficits, repetitive behaviors, and neuroinflammation.

The composition and diversity of gut microbiota significantly influence the immune system and are linked to various diseases, including inflammatory and allergy disorders. While considerable research has focused on exploring single bacterial species or consortia, the optimal strategies for microbiota-based therapeutics remain underexplored. Specifically, the comparative effectiveness of bacterial consortia versus individual species warrants further investigation. In our study, we assessed the impact of the bacterial consortium MPRO, comprising Lactiplantibacillus plantarum HY7712, Bifidobacterium animalis ssp. lactis HY8002, and Lacticaseibacillus casei HY2782, in comparison to its individual components. The administration of MPRO demonstrated enhanced therapeutic efficacy in experimental models of atopic dermatitis and inflammatory colitis when compared to single strains. MPRO exhibited the ability to dampen inflammatory responses and alter the gut microbial landscape significantly. Notably, MPRO administration led to an increase in intestinal CD103+CD11b+ dendritic cells, promoting the induction of regulatory T cells and the robust suppression of inflammation in experimental disease settings. Our findings advocate the preference for bacterial consortia over single strains in the treatment of inflammatory disorders, carrying potential clinical relevance.

Background The gut microbiota plays an essential role in mucosal immunity, with secretory immunoglobulin A (IgA) acting as a key effector in neutralizing pathogens and maintaining host-microbiota homeostasis. IgA production occurs via T cell-dependent (TD) and -independent pathways, with T follicular helper (Tfh) cells driving high-affinity, antigen-specific IgA responses. However, the specific microbial taxa and metabolites that regulate Tfh-mediated IgA responses under steady-state conditions remain poorly understood. This study investigated how gut microbiota-derived signals shape Tfh responses and IgA production, with implications for enhancing mucosal vaccine efficacy. Results We demonstrate that Peyer’s patches (PP)-derived Tfh cells exhibit superior IgA-inducing capacity compared to splenic Tfh cells. RNA sequencing revealed distinct transcriptional profiles in PP-Tfh cells, including upregulation of the genes associated with Tfh differentiation and activation ( Bcl6, Cd40lg, Maf ), T-B cell interactions ( Il21, Sh2d1a, Fyn ), and migration ( Ccr6, Cxcr5 ). Functionally, PP-Tfh cells formed larger T-B cell contact areas and induced significantly higher IgA secretion in co-culture than their splenic counterparts. Microbiota depletion experiments revealed that eliminating neomycin-depleted bacteria reduced fecal IgA levels and diminished PP-Tfh cell frequencies. Fecal microbiota transplantation from neomycin-treated mice restored both IgA production and Tfh responses in germ-free (GF) mice. Bioinformatic analysis (PICRUSt2 and LEfSe) identified butyrate-producing Lachnospiraceae and Ruminococcaceae as key drivers of the Tfh-IgA axis. Butyrate supplementation enhanced Tfh differentiation and IgA⁺ germinal center B cell development in vitro and increased fecal IgA levels in vivo. Mechanistically, butyrate promoted IgA production via GPR43 signaling, as its effect was lost in co-cultures with Gpr43 ⁻/⁻ Tfh cells. Moreover, treatment with tributyrin, a butyrate prodrug, enhanced vaccine-induced IgA and protected mice against Salmonella Typhimurium infection, reducing bacterial burden and tissue damage. These findings define a functional microbiota-Tfh-IgA axis sustained by neomycin-depleted, butyrate-producing bacteria. Conclusions Our study underscores the crucial role of the gut microbiota, particularly neomycin-depleted butyrate producing taxa, in regulating PP-Tfh cell function and IgA production. Butyrate emerges as a metabolite linking microbial metabolism to Tfh differentiation and IgA class switching. Together, these findings establish a microbiota-metabolite-Tfh cell axis essential for mucosal immune homeostasis and suggest novel strategies for enhancing vaccine efficacy and protection against enteric infections. 65SkT5T5U4s1JHPzYWZphR Video Abstract

Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus   plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8 + T cell response, and triggers macrophage ‘nutritional immunity’ to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into ‘oncobiotics’ for a multi-layered approach to cancer therapy. Here the authors show that a heteropolysaccharide from a commensal bacteria commonly found in the Korean food kimchi is able to bolster antitumor immune responses by instructing tumor-associated macrophages to release lipocalin-2, which sequesters iron away from tumor cells contributing to the immune response to attack these cells.

Follicular regulatory T (Tfr) cells maintain immune homeostasis by suppressing excessive germinal center (GC) responses. However, the molecular mechanisms governing Tfr differentiation remain incompletely understood. Here, we identify interleukin-6 (IL-6) as a key regulator of Tfr generation. IL-6/IL-6Rα signaling promotes the differentiation of regulatory T cells (Treg) into Tfr cells by inducing CCAAT/enhancer binding protein α (C/EBPα), which binds the Bcl6 and Cxcr5 promoters in Tfr cells. Treg-specific deletion of C/EBPα in mice impairs Tfr differentiation, resulting in hyperactive GC responses and exacerbated pathology in mouse models of systemic lupus erythematosus (SLE) and HDM-induced allergy. In humans, in silico perturbation of CEBPA in Tregs disrupts the Tfr differentiation trajectory. Furthermore, CEBPA expression in Tregs, but not total CD4 T cells, from patients with SLE negatively correlates with disease activity (SLEDAI). Thus, these findings establish the IL-6-C/EBPα axis as a critical mechanism driving Tfr differentiation to restrain pathogenic humoral immunity.

The electroreduction of carbon dioxide offers a promising avenue to produce valuable fuels and chemicals using greenhouse gas carbon dioxide as the carbon feedstock. Because industrial carbon dioxide point sources often contain numerous contaminants, such as nitrogen oxides, understanding the potential impact of contaminants on carbon dioxide electrolysis is crucial for practical applications. Herein, we investigate the impact of various nitrogen oxides, including nitric oxide, nitrogen dioxide, and nitrous oxide, on carbon dioxide electroreduction on three model electrocatalysts (i.e., copper, silver, and tin). We demonstrate that the presence of nitrogen oxides (up to 0.83%) in the carbon dioxide feed leads to a considerable Faradaic efficiency loss in carbon dioxide electroreduction, which is caused by the preferential electroreduction of nitrogen oxides over carbon dioxide. The primary products of nitrogen oxides electroreduction include nitrous oxide, nitrogen, hydroxylamine, and ammonia. Despite the loss in Faradaic efficiency, the electrocatalysts exhibit similar carbon dioxide reduction performances once a pure carbon dioxide feed is restored, indicating a negligible long-term impact of nitrogen oxides on the catalytic properties of the model catalysts. Understanding the impact of nitrogen oxides, common contaminants in CO 2 emission from industries is a key to commercializing CO 2 electrolysis technologies. Here, the authors conduct an investigation of CO 2 electroreduction on copper, silver, and tin catalysts in the presence of nitric oxide, nitrogen dioxide, or nitrous oxide.

To enhance our understanding of the impact of galaxy mergers on the kinematics of early-type galaxies (ETGs), we examine differences in specific stellar angular momentum within the half-light radius ( λRe ) among ETGs with different types of tidal features and those without such features. This is accomplished by categorizing tidal features, which serve as direct evidence of recent mergers, into shells, streams, and tails, through deep images from the DESI Legacy Survey, and by using MaNGA data for the analysis of the kinematics of 1244 ETGs at z < 0.055. We find that ETGs with tidal features typically have reduced λRe values that are lower by 0.12 dex than ETGs without tidal features. ETGs with shells contribute most to the reduction in λRe . Consequently, nearly half of ETGs with shells are classified as slow rotators, a fraction that is more than twice as high as that of ETGs with tails or streams, and over three times higher than that of ETGs without tidal features. These trends generally remain valid even when ETGs are divided into several mass bins. Our findings support the idea that radial mergers, which are more effective at reducing λRe than circular mergers, are more closely associated with the formation of shells rather than streams or tails. The detection of shells in slightly more massive ETGs compared to streams and tails may be attributed to the fact that massive satellite galaxies are more likely to be accreted through radial orbits, due to the nature of dynamical friction.

Electrocatalytic conversion of carbon monoxide (CO) is being actively developed as a key component for tandem CO 2 electrolysis. Great effort has been devoted to engineering CO reduction electrocatalysts for better multicarbon product selectivity. However, less work has focused on other performance parameters that are crucial for commercializing CO electrolysis, such as liquid product concentration and purity. Here, we present an internally coupled purification strategy to substantially improve the acetate concentration and purity in CO electrolysis. This strategy utilizes an alkaline-stable anion exchange membrane with high ethanol permeability and a selective ethanol partial oxidation anode to control the CO reduction product stream. We demonstrate stable 120-h continuous operation of the CO electrolyser at a current density of 200 mA cm −2 and a full-cell potential of <2.3 V, continuously producing a 1.9 M acetate product stream with a purity of 97.7%. The acetate stream was further improved to a concentration of 7.6 M at >99% purity by tuning the reaction conditions. Finally, a techno-economic analysis shows that a highly concentrated liquid product stream is essential to reduce the energy consumption of product separation. CO can be reduced electrocatalytically on Cu-based electrodes to acetate and ethanol; however, formation of mixed product streams creates a separation issue. Here, a selective anode for ethanol partial oxidation and an anion exchange membrane with high ethanol permeability are incorporated into an electrolyser to generate pure acetate (>99%) at high concentration (up to 7.6 M).

We present a methodology for constructing a mock galaxy catalog for the All-sky SPECtroscopic survey of nearby galaxies (A-SPEC) using the Machine-assisted Semi-Simulation Model. The model is trained on the cosmological magnetohydrodynamical simulation IllustrisTNG to predict baryonic properties of subhalos from dark-matter-only features and is applied to our own N-body simulation tailored to satisfy the requirements of A-SPEC. We have improved the model's accuracy by introducing additional features such as subhalo anisotropy parameters and modified definitions of the subhalo environment, which result in the coefficient of determination R2 = 0.96, 0.90, 0.70, 0.79 for stellar mass, gas mass, star formation rate, and gas metallicity, respectively. The resulting mock galaxies reproduce the luminosity-dependent clustering of the target galaxies when tuned to match the number density. We discuss avenues for further improvement, including the role of environment in the predictions. We release the mock galaxy catalog with the baryonic properties predicted from the model.