Gut microbiota-derived short-chain fatty acids(SCFAs)impact asthma outcomes,highlighting the importance of understanding the disease mechanisms through the gut-lung axis.In this study,we identified that among SCFAs,bu...Gut microbiota-derived short-chain fatty acids(SCFAs)impact asthma outcomes,highlighting the importance of understanding the disease mechanisms through the gut-lung axis.In this study,we identified that among SCFAs,butyrate uniquely alleviates asthma through specifically inhibiting a newly identified pathogenic T follicular helper(Tfh)cell subset,Tfh13 cells.Tfh13 cell depletion(Il13^(Cre)/+Bcl6^(fl/fl))or adoptive transfer of Tfh13 cells in an OVA-induced asthma model conclusively demonstrated their indispensable role in driving anaphylactic IgE production and asthma pathogenesis.Mechanistically,the inhibitory function of butyrate on Tfh13 cells is mediated by the interaction between butyrate and G-protein coupled receptor 43(GPR43),leading to the suppression of p38 MAPK/NF-κB signaling in Tfh13 cells.To address the clinically observed deficiency of butyrate in patients with asthma and recapitulated in murine models,we developed a novel therapeutic strategy using a butyrate-yielding diet enriched with butylated high amylose maize starch(HAMSB).Remarkably,supplementation with HAMSB diet in murine and humanized asthma models significantly reduced Tfh13 cell frequencies and anaphylactic IgE levels,leading to significantly improved disease outcomes.Our findings not only unveil a novel mechanism underlying butyrate-mediated asthma alleviation,termed the butyrate-Tfh13-IgE axis,but also propose a clinically translatable dietary intervention strategy targeting microbial metabolites for stopping asthma.展开更多
To the Editor:Immunoglobulin A nephropathy(IgAN)is the most common form of primary glomerulonephritis worldwide.[1]Observational studies suggest a link between circulating inflammatory cytokines and IgAN.[2]However,th...To the Editor:Immunoglobulin A nephropathy(IgAN)is the most common form of primary glomerulonephritis worldwide.[1]Observational studies suggest a link between circulating inflammatory cytokines and IgAN.[2]However,the causal roles of these cytokines in IgAN are not yet systematically understood.Mendelian randomization(MR)uses genetic variants as instrumental variables(IVs)in observational epidemiology to infer the causality of modifiable disease risk factors.Since genetic alleles are randomly assigned at conception,this method reduces confounding and reverse causation and has been widely used to explore causal relationships between exposures and diseases.This study explored the causal relationship between circulating inflammatory cytokines and IgAN using MR and identified upstream systemic regulators.展开更多
To the Editor:Patients with severe persistent asthma experience greater morbidity with more impairment in quality of life despite higher use of health care resources and being treated with existing asthma treatments s...To the Editor:Patients with severe persistent asthma experience greater morbidity with more impairment in quality of life despite higher use of health care resources and being treated with existing asthma treatments such as inhaled corticosteroids and b-agonists,and sometimes oral corticosteroid(OCS)therapy.Type-2(T2)high asthma has been identified as a phenotype that responds to targeted T2 biologic therapies such as anti-IgE,anti-interleukin(IL)5,or anti-IL5Ra and anti-IL4Ra monoclonal antibodies,which are currently available in Europe and North America,and are currently introduced in the rest of the world.[1]展开更多
Telomeres protect the ends of chromosomes and are important biomarkers of cellular aging.The mechanism of telomere elongation in T cells is not clear.A recent study revealed that memory CD4+T cells can acquire telomer...Telomeres protect the ends of chromosomes and are important biomarkers of cellular aging.The mechanism of telomere elongation in T cells is not clear.A recent study revealed that memory CD4+T cells can acquire telomeric DNA transferred via vesicles from antigen-presenting cells,which inhibits T-cell senescence and promotes T-cell expansion and long-lived immunity.展开更多
基金supported by the General Program of the National Natural Science Foundation of China(81971493)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(82121002)+1 种基金the Major Program of National Natural Science Foundation of China(82130050,82330053)the Innovative Research Team of High-level Local Universities in Shanghai。
文摘Gut microbiota-derived short-chain fatty acids(SCFAs)impact asthma outcomes,highlighting the importance of understanding the disease mechanisms through the gut-lung axis.In this study,we identified that among SCFAs,butyrate uniquely alleviates asthma through specifically inhibiting a newly identified pathogenic T follicular helper(Tfh)cell subset,Tfh13 cells.Tfh13 cell depletion(Il13^(Cre)/+Bcl6^(fl/fl))or adoptive transfer of Tfh13 cells in an OVA-induced asthma model conclusively demonstrated their indispensable role in driving anaphylactic IgE production and asthma pathogenesis.Mechanistically,the inhibitory function of butyrate on Tfh13 cells is mediated by the interaction between butyrate and G-protein coupled receptor 43(GPR43),leading to the suppression of p38 MAPK/NF-κB signaling in Tfh13 cells.To address the clinically observed deficiency of butyrate in patients with asthma and recapitulated in murine models,we developed a novel therapeutic strategy using a butyrate-yielding diet enriched with butylated high amylose maize starch(HAMSB).Remarkably,supplementation with HAMSB diet in murine and humanized asthma models significantly reduced Tfh13 cell frequencies and anaphylactic IgE levels,leading to significantly improved disease outcomes.Our findings not only unveil a novel mechanism underlying butyrate-mediated asthma alleviation,termed the butyrate-Tfh13-IgE axis,but also propose a clinically translatable dietary intervention strategy targeting microbial metabolites for stopping asthma.
基金supported by the Multidisciplinary Clinical Research Innovation Project(No.CYDXK202213)the Natural Science Foundation of China(No.62476181)+1 种基金the Jinzhongzi project of Beijing Chao-Yang Hospital(No.CYJZ202203)the National Natural Science Foundation of China(No.82170686).
文摘To the Editor:Immunoglobulin A nephropathy(IgAN)is the most common form of primary glomerulonephritis worldwide.[1]Observational studies suggest a link between circulating inflammatory cytokines and IgAN.[2]However,the causal roles of these cytokines in IgAN are not yet systematically understood.Mendelian randomization(MR)uses genetic variants as instrumental variables(IVs)in observational epidemiology to infer the causality of modifiable disease risk factors.Since genetic alleles are randomly assigned at conception,this method reduces confounding and reverse causation and has been widely used to explore causal relationships between exposures and diseases.This study explored the causal relationship between circulating inflammatory cytokines and IgAN using MR and identified upstream systemic regulators.
基金supported by grants from AstraZeneca,China,and the National Natural Science Foundation of China(No.82070026).
文摘To the Editor:Patients with severe persistent asthma experience greater morbidity with more impairment in quality of life despite higher use of health care resources and being treated with existing asthma treatments such as inhaled corticosteroids and b-agonists,and sometimes oral corticosteroid(OCS)therapy.Type-2(T2)high asthma has been identified as a phenotype that responds to targeted T2 biologic therapies such as anti-IgE,anti-interleukin(IL)5,or anti-IL5Ra and anti-IL4Ra monoclonal antibodies,which are currently available in Europe and North America,and are currently introduced in the rest of the world.[1]
文摘Telomeres protect the ends of chromosomes and are important biomarkers of cellular aging.The mechanism of telomere elongation in T cells is not clear.A recent study revealed that memory CD4+T cells can acquire telomeric DNA transferred via vesicles from antigen-presenting cells,which inhibits T-cell senescence and promotes T-cell expansion and long-lived immunity.
