Unravelling the anionic stability of an ether-based electrolyte with a hard carbon or metallic sodium anode for high-performance sodium-ion batteries.

In hard carbon (HC) anodes, elucidating the relationship between the solid electrolyte interphase formation and the solvated Na+ co-intercalation mechanism is crucial, particularly considering different anionic salts in ether-based electrolytes. Here, we comprehensively explore the impact of different anionic salts on the electrochemical performance of HC/Na half-cell and elucidate the underlying mechanism through experimental studies and theoretical calculations. The surface morphology of the HC anode and its interphasial property are further investigated to evaluate the differences endowed by the presence of various anionic salts in diglyme (2G). The HC/Na half-cells with NaPF6-2G and sodium trifluoromethanesulfonate (NaCF3SO3)-2G display superior electrochemical performance with faster kinetics and lower interfacial resistance than those with NaClO4-2G, sodium bis-(fluorosulfonyl) imide (NaFSI)-2G and sodium bis-(trifluoromethanesulfonyl) imide (NaTFSI)-2G. NaClO4-2G forms a relatively thick interphase layer with high resistance at the electrode/electrolyte interface owing to its insufficient stability. NaFSI-2G and NaTFSI-2G exhibit severe side reactions with Na metal, producing a thick interphase layer on the HC surface with high interfacial resistance from excess electrolyte decomposition, thus deteriorating the electrochemical performance. In summary, the study on the stability of different anionic salts in ether-based electrolyte for the HC anode with the intercalation mechanism provides valuable insights for screening appropriate conductive salts for high-performance sodium-ion batteries, especially when considering Na metal counter/reference electrodes.

Opposite effects of soil pH on bacteria and fungi ß diversity in forests at a continental scale.

Soil microbial diversity is crucial for regulating biogeochemical cycles, including soil carbon (C) dynamics and nutrient cycling. However, how climate, plants, and soil properties influence the microbiome in forests remains unclear, especially at the continental scale, hindering us to better understand forest C-climate change feedback. Here, we investigated the spatial patterns of microbial diversity across China's forests and explored the controlling factors of microbial ß diversity and network complexity. Our results showed that soil pH strongly influenced bacterial and fungal ß diversity compared to climate, soil nutrient and plant properties. To further investigate the environmental preference of the microbial networks, we classified the amplicon sequence variants (ASVs) into five groups ranging from acidic to alkaline soils. Co-occurrence network analysis revealed that the topological structure of the bacterial network (e.g., edge and degree) increased with pH and was negatively correlated with ß diversity but not for fungal diversity. Soil fungi exhibited higher ß diversity and network complexity (i.e., degree and betweenness) than bacteria in acidic soils (pH < 5.1), and vice versa in neutral and alkaline soils (pH > 5.5). Within the pH range of 5.1-5.5, the bacterial-fungal network displayed the highest network complexity with the lowest fungal ß diversity, and significant positive correlations were found between fungal ß diversity and soil properties. In addition, bacterial growth in acidic soil (pH < 5.5) showed positive correlations with acid phosphatase (AP), but negative ones with ß-1,4-glucosidase (BG), and vice versa in neutral and alkaline soils (pH > 5.5). Furthermore, 46 bacterial core species were identified, and their abundance had significant correlation with soil pH. These findings highlight the critical role of soil pH in driving soil microbial ß diversity across China's forests and reveal the effects of pH thresholds on changes in the soil microbial network and core species.

USP25 Promotes the Antimycobacterial Response of Macrophages Through Stabilizing B-Raf and C-Raf.

Ubiquitin-specific peptidase 25 (USP25) is one of the best-characterized deubiquitinating enzymes and plays a vital regulatory role in various biological processes, especially in cancer development and immune regulation. However, the exact role of USP25 and its underlying mechanisms in macrophage activation and immunogenicity during Mycobacterium tuberculosis infection remain unclear. In this study, we found that M tuberculosis infection induced USP25 expression in human and mouse macrophages. In particular, USP25 expression is elevated in multiple cell types, especially monocytes, in patients with tuberculosis. Additionally, USP25 deficiency in macrophages and mice resulted in compromised immunity against M tuberculosis infection, accompanied by reduced expressions of various proinflammatory cytokines and chemokines. Mechanistically, USP25 in macrophages promoted the activation of the ERK signaling pathway through deubiquitination and stabilization of B-Raf and C-Raf. These findings collectively suggest the critical roles of USP25 in M tuberculosis infection and its potential as a therapeutic target.

RNF213 promotes Treg cell differentiation by facilitating K63-linked ubiquitination and nuclear translocation of FOXO1.

Autoreactive CD4+ T helper cells are critical players that orchestrate the immune response both in multiple sclerosis (MS) and in other neuroinflammatory autoimmune diseases. Ubiquitination is a posttranslational protein modification involved in regulating a variety of cellular processes, including CD4+ T cell differentiation and function. However, only a limited number of E3 ubiquitin ligases have been characterized in terms of their biological functions, particularly in CD4+ T cell differentiation and function. In this study, we found that the RING finger protein 213 (RNF213) specifically promoted regulatory T (Treg) cell differentiation in CD4+ T cells and attenuated autoimmune disease development in an FOXO1-dependent manner. Mechanistically, RNF213 interacts with Forkhead Box Protein O1 (FOXO1) and promotes nuclear translocation of FOXO1 by K63-linked ubiquitination. Notably, RNF213 expression in CD4+ T cells was induced by IFN-ß and exerts a crucial role in the therapeutic efficacy of IFN-ß for MS. Together, our study findings collectively emphasize the pivotal role of RNF213 in modulating adaptive immune responses. RNF213 holds potential as a promising therapeutic target for addressing disorders associated with Treg cells.

A transition from arbuscular to ectomycorrhizal forests halts soil carbon sequestration during subtropical forest rewilding.

Ecological succession and restoration rapidly promote multiple dimensions of ecosystem functions and mitigate global climate change. However, the factors governing the limited capacity to sequester soil organic carbon (SOC) in old forests are poorly understood. Ecological theory predicts that plants and microorganisms jointly evolve into a more mutualistic relationship to accelerate detritus decomposition and nutrient regeneration in old than young forests, likely explaining the changes in C sinks across forest succession or rewilding. To test this hypothesis, we conducted a field experiment of root-mycorrhizal exclusion in successional subtropical forests to investigate plant-decomposer interactions and their effects on SOC sequestration. Our results showed that SOC accrual rate at the 0-10 cm soil layer was 1.26 mg g-1 yr-1 in early-successional arbuscular mycorrhizal (AM) forests, which was higher than that in the late-successional ectomycorrhizal (EcM) forests with non-significant change. A transition from early-successional AM to late-successional EcM forests increase fungal diversity, especially EcM fungi. In the late-successional forests, the presence of ectomycorrhizal hyphae promotes SOC decomposition and nutrient cycle by increasing soil nitrogen and phosphorus degrading enzyme activity as well as saprotrophic microbial richness. Across early- to late-successional forests, mycorrhizal priming effects on SOC decomposition explain a slow-down in the capacity of older forests to sequester soil C. Our findings suggest that a transition from AM to EcM forests supporting greater C decomposition can halt the capacity of forests to provide nature-based global climate change solutions.

Mycorrhizal associations relate to stable convergence in plant-microbial competition for nitrogen absorption under high nitrogen conditions.

Nitrogen (N) immobilization (Nim, including microbial N assimilation) and plant N uptake (PNU) are the two most important pathways of N retention in soils. The ratio of Nim to PNU (hereafter Nim:PNU ratio) generally reflects the degree of N limitation for plant growth in terrestrial ecosystems. However, the key factors driving the pattern of Nim:PNU ratio across global ecosystems remain unclear. Here, using a global data set of 1018 observations from 184 studies, we examined the relative importance of mycorrhizal associations, climate, plant, and soil properties on the Nim:PNU ratio across terrestrial ecosystems. Our results show that mycorrhizal fungi type (arbuscular mycorrhizal (AM) or ectomycorrhizal (EM) fungi) in combination with soil inorganic N mainly explain the global variation in the Nim:PNU ratio in terrestrial ecosystems. In AM fungi-associated ecosystems, the relationship between Nim and PNU displays a weaker negative correlation (r = -.06, p < .001), whereas there is a stronger positive correlation (r = .25, p < .001) in EM fungi-associated ecosystems. Our meta-analysis thus suggests that the AM-associated plants display a weak interaction with soil microorganisms for N absorption, while EM-associated plants cooperate with soil microorganisms. Furthermore, we find that the Nim:PNU ratio for both AM- and EM-associated ecosystems gradually converge around a stable value (13.8 ± 0.5 for AM- and 12.1 ± 1.2 for EM-associated ecosystems) under high soil inorganic N conditions. Our findings highlight the dependence of plant-microbial interaction for N absorption on both plant mycorrhizal association and soil inorganic N, with the stable convergence of the Nim:PNU ratio under high soil N conditions.

Correction: USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

[This corrects the article DOI: 10.1371/journal.ppat.1011480.].

Research progress of novel bio-denitrification technology in deep wastewater treatment.

Excessive nitrogen emissions are a major contributor to water pollution, posing a threat not only to the environment but also to human health. Therefore, achieving deep denitrification of wastewater is of significant importance. Traditional biological denitrification methods have some drawbacks, including long processing times, substantial land requirements, high energy consumption, and high investment and operational costs. In contrast, the novel bio-denitrification technology reduces the traditional processing time and lowers operational and maintenance costs while improving denitrification efficiency. This technology falls within the category of environmentally friendly, low-energy deep denitrification methods. This paper introduces several innovative bio-denitrification technologies and their combinations, conducts a comparative analysis of their denitrification efficiency across various wastewater types, and concludes by outlining the future prospects for the development of these novel bio-denitrification technologies.

Co-application of biochar and organic amendments on soil greenhouse gas emissions: A meta-analysis.

Biochar has been shown to reduce soil greenhouse gas (GHG) and increase nutrient retention in soil; however, the interaction between biochar and organic amendments on GHG emissions remain largely unclear. In this study, we collected 162 two-factor observations to explore how biochar and organic amendments jointly affect soil GHG emissions. Our results showed that biochar addition significantly increased soil CO2 emission by 8.62 %, but reduced CH4 and N2O emissions by 27.0 % and 23.9 %, respectively. Meanwhile, organic amendments and the co-application with biochar resulted in an increase of global warming potential based on the 100-year time horizon (GWP100) by an average of 18.3 % and 26.1 %. More importantly, the interactive effect of biochar and organic amendments on CO2 emission was antagonistic (the combined effect was weaker than the sum of their individual effects), while additive on CH4 and N2O emissions. Additionally, our results suggested that when biochar is co-applied with organic amendments, soil GHG emissions were largely influenced by soil initial total carbon, soil texture, and biochar feedstocks. Our work highlights the important interactive effects of biochar and organic amendments on soil GHG emissions, and provides new insights for promoting ecosystem sustainability as well as mitigating future climate change.

USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

Deubiquitinating enzymes (DUBs) regulate antiviral immune response through targeting DNA sensor signaling pathway members. As one of the DNA sensors, interferon (IFN)-γ inducible protein 16 (IFI16) play a major role in response to virus infections through activating the canonical STING/TBK-1/IRF3 signaling pathway. Only a few studies discuss the function of DUBs in IFI16-mediated antiviral response. Ubiquitin-specific protease 12 (USP12), which is one of the major members of the USP family, participates in various biological functions. However, whether USP12 regulates the nucleic acid sensor to modulate antiviral immune responses has not yet been elucidated. In this study, we found that knockout or knockdown of USP12 impaired the HSV-1-induced expressions of IFN-ß, CCL-5, IL-6, and downstream interferon-stimulated genes (ISGs). Moreover, USP12 deficiency increased HSV-1 replication and host susceptibility to HSV-1 infection. Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity, thereby maintaining IFI16 stability and promoting IFI16-STING-IRF3- and p65-mediated antiviral signaling. Overall, our findings demonstrate an essential role of USP12 in DNA-sensing signaling and contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

The E3 ligase HERC5 promotes antimycobacterial responses in macrophages by ISGylating the phosphatase PTEN.

Innate immune signaling in macrophages during viral infection is regulated by ISGylation, the covalent attachment of the ubiquitin-like protein interferon-stimulated gene 15 (ISG15) to protein targets. Here, we explored the role of ISGylation in the macrophage response to infection with Mycobacterium tuberculosis. In human and mouse macrophages, the E3 ubiquitin ligases HERC5 and mHERC6, respectively, mediated the ISGylation of the phosphatase PTEN, which promoted its degradation. The decreased abundance of PTEN led to an increase in the activity of the PI3K-AKT signaling pathway, which stimulated the synthesis of proinflammatory cytokines. Bacterial growth was increased in culture and in vivo when human or mouse macrophages were deficient in the major E3 ISG15 ligase. The findings expand the role of ISGylation in macrophages to antibacterial immunity and suggest that HERC5 signaling may be a candidate target for adjunct host-directed therapy in patients with tuberculosis.

Plant growth strategy determines the magnitude and direction of drought-induced changes in root exudates in subtropical forests.

Root exudates are an important pathway for plant-microbial interactions and are highly sensitive to climate change. However, how extreme drought affects root exudates and the main components, as well as species-specific differences in response magnitude and direction, are poorly understood. In this study, root exudation rates of total carbon (C) and its components (e.g., sugar, organic acid, and amino acid) were measured under the control and extreme drought treatments (i.e., 70% throughfall reduction) by in situ collection of four tree species with different growth rates in a subtropical forest. We also quantified soil properties, root morphological traits, and mycorrhizal infection rates to examine the driving factors underlying variations in root exudation. Our results showed that extreme drought significantly decreased root exudation rates of total C, sugar, and amino acid by 17.8%, 30.8%, and 35.0%, respectively, but increased root exudation rate of organic acid by 38.6%, which were largely associated with drought-induced changes in tree growth rates, root morphological traits, and mycorrhizal infection rates. Specifically, trees with relatively high growth rates were more responsive to drought for root exudation rates compared with those with relatively low growth rates, which were closely related to root morphological traits and mycorrhizal infection rates. These findings highlight the importance of plant growth strategy in mediating drought-induced changes in root exudation rates. The coordinations among root exudation rates, root morphological traits, and mycorrhizal symbioses in response to drought could be incorporated into land surface models to improve the prediction of climate change impacts on rhizosphere C dynamics in forest ecosystems.

Elevated Insulin-Like Growth Factor-1-Induced Female Rats Perpetuate the Polycystic Ovary Syndrome Phenotype: Pathological Mechanism of Insulin-Like Growth Factor-1 in Polycystic Ovary Syndrome.

OBJECTIVES: This study was designated to establish a polycystic ovary syndrome (PCOS) rat model with recombinant human insulin-like growth factor-1 (RH-IGF-1). We made assessment on the characteristics of hyperinsulinemia and hyperandrogenism in the rat model. DESIGN: This study performed the characteristics of PCOS upon RH-IGF-1 injection and evaluated the disease process of PCOS syndrome caused by the insulin-resistant pathological condition of IGF-1 based on the comparative study of in vivo test. SETTING: The experiment was conducted in the experimental research center of Yinzhou NO.2 hospital, Ningbo, Zhejiang Province, China. MATERIALS AND METHODS: Thirty-four female Sprague Dawley immature rats aged 21 days were randomly divided into two groups. Those treated with RH-IGF-1 2 mg/100 g daily were in RH-IGF-1 group (n = 20), and those with 0.9% sodium chloride 0.2 mL/100 g daily were in the saline group (n = 14). The experiment was carried out in two stages. In stage I, rats were anesthetized upon the first estrous cycle in the saline group with tissue and blood samples collected (n = 7), and rats in the RH-IGF-1-treated group were anesthetized on the 5th day after vaginal opening (VO) (n = 10). In stage II, rats in the saline group were anesthetized after three complete cycles (n = 7), meanwhile, while on the 15th day after VO (n = 10) for those in the RH-IGF-1 group. RESULTS: We have found that compared with the control group, rats injected with RH-IGF-1 expressed an early VO, disordered estrous cycle, polycystic ovaries, and significantly increased ovarian weight/body weight ratio. And from the perspective of hormone secretion, their androgen increased significantly and the insulin resistance index also elevated distinctly, possessing main characteristics similar to PCOS. LIMITATIONS: In this study, we were limited by the inability to examine IGF-1 in hypothalamus. IGF-1 in hypothalamus and in vitro experiments would be taken into consideration for further study in the future. CONCLUSIONS: These findings suggest that IGF-1 may be a key factor in the pathogenesis of PCOS, and the increase of androgen may be the pathological result, not the cause of PCOS.

Global systematic review with meta-analysis shows that warming effects on terrestrial plant biomass allocation are influenced by precipitation and mycorrhizal association.

Biomass allocation in plants is fundamental for understanding and predicting terrestrial carbon storage. Yet, our knowledge regarding warming effects on root: shoot ratio (R/S) remains limited. Here, we present a meta-analysis encompassing more than 300 studies and including angiosperms and gymnosperms as well as different biomes (cropland, desert, forest, grassland, tundra, and wetland). The meta-analysis shows that average warming of 2.50 °C (median = 2 °C) significantly increases biomass allocation to roots with a mean increase of 8.1% in R/S. Two factors associate significantly with this response to warming: mean annual precipitation and the type of mycorrhizal fungi associated with plants. Warming-induced allocation to roots is greater in drier habitats when compared to shoots (+15.1% in R/S), while lower in wetter habitats (+4.9% in R/S). This R/S pattern is more frequent in plants associated with arbuscular mycorrhizal fungi, compared to ectomycorrhizal fungi. These results show that precipitation variability and mycorrhizal association can affect terrestrial carbon dynamics by influencing biomass allocation strategies in a warmer world, suggesting that climate change could influence belowground C sequestration.

Grazing and global change factors differentially affect biodiversity-ecosystem functioning relationships in grassland ecosystems.

Grazing and global change (e.g., warming, nitrogen deposition, and altered precipitation) both contribute to biodiversity loss and alter ecosystem structure and functioning. However, how grazing and global change interactively influence plant diversity and ecosystem productivity, and their relationship remains unclear at the global scale. Here, we synthesized 73 field studies to quantify the individual and/or interactive effects of grazing and global change factors on biodiversity-productivity relationship in grasslands. Our results showed that grazing significantly reduced plant richness by 3.7% and aboveground net primary productivity (ANPP) by 29.1%, but increased belowground net primary productivity (BNPP) by 9.3%. Global change factors, however, decreased richness by 8.0% but increased ANPP and BNPP by 13.4% and 14.9%, respectively. Interestingly, the strength of the change in biodiversity in response to grazing was positively correlated with the strength of the change in BNPP. Yet, global change flipped these relationships from positive to negative even when combined with grazing. These results indicate that the impacts of global change factors are more dominant than grazing on the belowground biodiversity-productivity relationship, which is contrary to the pattern of aboveground one. Therefore, incorporating global change factors with herbivore grazing into Earth system models is necessary to accurately predict climate-grassland carbon cycle feedbacks in the Anthropocene.

UCHL1 Promoted Polarization of M1 Macrophages by Regulating the PI3K/AKT Signaling Pathway.

BACKGROUND: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear. METHODS: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice. RESULTS: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states. CONCLUSION: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.

Differential effects of nitrogen vs. phosphorus limitation on terrestrial carbon storage in two subtropical forests: A Bayesian approach.

Nitrogen (N) and phosphorus (P) have been demonstrated to limit terrestrial carbon (C) storage in terrestrial ecosystems. However, the reliable indicator to infer N and P limitation are still lacking, especially in subtropical forests. Here we used a terrestrial ecosystem (TECO) model framework in combination with a Bayesian approach to evaluate effects of nutrient limitation from added N/P processes and data sets on C storage capacities in two subtropical forests (Tiantong and Qianyanzhou [QYZ]). Three of the six simulation experiments were developed with assimilating data (TECO C model with C data [C-C], TECO C-N coupling model with C and N data [CN-CN], and TECO C-N-P model with C, N, and P data [CNP-CNP]), and the other three ones were simulated without assimilating data (C-only, CN-only, and CNP-only). We found that P dominantly constrained C storage capacities in Tiantong (42%) whereas N limitation decreased C storage projections in QYZ (44%). Our analysis indicated that the stoichiometry of wood biomass and soil microbe (e.g., N:P ratio) were more sensitive indicators of N or P limitation than that of other pools. Furthermore, effects of P-induced limitation were mainly on root biomass by additional P data and on both metabolic litter and soil organic carbon (SOC) by added P processes. N-induced effects were mainly from added N data that limited plant non-photosynthetic tissues (e.g., woody biomass and litter). The different effects of N and P modules on C storage projections reflected the diverse nutrient acquisition strategies associated with stand ages and plant species under nutrient stressed environment. These findings suggest that the interaction between plants and microorganisms regulate effects of nutrient availability on ecosystem C storage, and stoichiometric flexibility of N and P in plant and soil C pools could improve the representation of N and P limitation in terrestrial ecosystem models.

USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10.

Deubiquitinases (DUBs) regulate diverse biological processes and represent a novel class of drug targets. However, the biological function of only a small fraction of DUBs, especially in adaptive immune response regulation, is well-defined. In this study, we identified DUB ubiquitin-specific peptidase 12 (USP12) as a critical regulator of CD4+ T cell activation. USP12 plays an intrinsic role in promoting the CD4+ T cell phenotype, including differentiation, activation, and proliferation. Although USP12-deficient CD4+ T cells protected mice from autoimmune diseases, the immune response against bacterial infection was subdued. USP12 stabilized B cell lymphoma/leukemia 10 (BCL10) by deubiquitinating, and thereby activated the NF-κB signaling pathway. Interestingly, this USP12 regulatory mechanism was identified in CD4+ T cells, but not in CD8+ T cells. Our study results showed that USP12 activated CD4+ T cell signaling, and targeting USP12 might help develop therapeutic interventions for treating inflammatory diseases or pathogen infections.

ß-Arrestin 2 Regulates Inflammatory Responses against Mycobacterium tuberculosis Infection through ERK1/2 Signaling.

Mycobacterium tuberculosis, the pathogen that causes tuberculosis, exhibits complex host-pathogen interactions. Pattern recognition receptors and their downstream signaling pathways play crucial roles in determining the outcome of infection. In particular, the scaffold protein ß-arrestin 2 mediates downstream signaling of G protein-coupled receptors. However, the role of ß-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that ß-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis infection upregulated ß-arrestin 2 expression in human macrophages, and silencing of ß-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-α. ß-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis infection. Furthermore, ß-arrestin 2 transcriptionally regulates TNF-α by binding to CREB1. These observations revealed that the upregulation of ß-arrestin 2 is critical for M. tuberculosis to escape immune surveillance through an unknown mechanism. Our research offers a novel interference modality to enhance the immune response against tuberculosis by targeting ß-arrestin 2 to modulate the TLR2-ß-arrestin 2-ERK1/2-CREB1-TNF-α regulatory axis.

Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase-dependent manner.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.