Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn...Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn's disease3,oesophagitis4 and multiple sclerosis5,6,and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence,in part by forming persistent pathogenic memory.Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7.Chronic rhinosinusitis affects more than 10%of the general population8.Among these patients,20-25%would develop nasal polyps,which often require repeated surgical resections owing to a high incidence of recurrence9.Whereas abundant T cells infiltrate the nasal polyps tissue10,11,T cell subsets that drive the disease pathology and promote recurrence are not fully understood.By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries,here we report that persistent CD8^(+)T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence,and these cells characteristically express the tryptase Granzyme K(GZMK).We find that GZMK cleaves many complement components,including C2,C3,C4 and C5,that collectively contribute to the activation of the complement cascade.GZMK-expressing CD8^(+)T cells participate in organized tertiary lymphoid structures,and tissue GZMK levels predict the disease severity and comorbidities better than well-established biomarkers such as eosinophilia and tissue interleukin-5.Using a mouse asthma model,we further show that GZMK-expressing CD8^(+)T cells exacerbate the disease in a manner dependent on the proteolytic activity of GZMK and complements.Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviates tissue pathology and restores lung function.Our work identifies a pathogenic CD8^(+)memory T cell subset that promotes tissue inflammation and recurrent airway diseases by the effector molecule GZMK and suggests GZMK as a potential therapeutic target.展开更多
Inverse vulcanized polymers(IVPs) that generated from elemental sulfur and smaller amounts of alkenes have found broad promising applications such as cathode materials for Li-S batteries, dynamic and repairable materi...Inverse vulcanized polymers(IVPs) that generated from elemental sulfur and smaller amounts of alkenes have found broad promising applications such as cathode materials for Li-S batteries, dynamic and repairable materials, optics applications, and metal sorption. However, their exploration in organic synthesis is still unprecedented. Here we first report the application of inverse vulcanized polymers in catalysis for organic transformations. A biomass-derived inverse vulcanized polymer(IVP-EAE) is found to be capable of catalyzing cross-coupling reactions in a transition-metal-free fashion under visible light.This method allows the direct C–H functionalization of pyrroles and N-arylacrylamides with(hetero)aryl halides, respectively, leading to the formation of two sets of structurally important scaffolds including pyrrole-containing biaryls and 3,3-disubstituted oxindoles with high selectivity. We anticipate this study will not only unveil the new potential of IVPs, but also offer a distinct type of catalysts for organic transformations.展开更多
文摘Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn's disease3,oesophagitis4 and multiple sclerosis5,6,and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence,in part by forming persistent pathogenic memory.Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7.Chronic rhinosinusitis affects more than 10%of the general population8.Among these patients,20-25%would develop nasal polyps,which often require repeated surgical resections owing to a high incidence of recurrence9.Whereas abundant T cells infiltrate the nasal polyps tissue10,11,T cell subsets that drive the disease pathology and promote recurrence are not fully understood.By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries,here we report that persistent CD8^(+)T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence,and these cells characteristically express the tryptase Granzyme K(GZMK).We find that GZMK cleaves many complement components,including C2,C3,C4 and C5,that collectively contribute to the activation of the complement cascade.GZMK-expressing CD8^(+)T cells participate in organized tertiary lymphoid structures,and tissue GZMK levels predict the disease severity and comorbidities better than well-established biomarkers such as eosinophilia and tissue interleukin-5.Using a mouse asthma model,we further show that GZMK-expressing CD8^(+)T cells exacerbate the disease in a manner dependent on the proteolytic activity of GZMK and complements.Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviates tissue pathology and restores lung function.Our work identifies a pathogenic CD8^(+)memory T cell subset that promotes tissue inflammation and recurrent airway diseases by the effector molecule GZMK and suggests GZMK as a potential therapeutic target.
基金the National Natural Science Foundation of China (NSFC, Nos. 22071024, 22271047)the Natural Science Foundation of Fujian Province (Nos.2021J06020, 2022J011121)the Top-Notch Young Talents Program of China, and the Science and Technology Project of Minjiang University (No.MJY21027) for generous financial support。
文摘Inverse vulcanized polymers(IVPs) that generated from elemental sulfur and smaller amounts of alkenes have found broad promising applications such as cathode materials for Li-S batteries, dynamic and repairable materials, optics applications, and metal sorption. However, their exploration in organic synthesis is still unprecedented. Here we first report the application of inverse vulcanized polymers in catalysis for organic transformations. A biomass-derived inverse vulcanized polymer(IVP-EAE) is found to be capable of catalyzing cross-coupling reactions in a transition-metal-free fashion under visible light.This method allows the direct C–H functionalization of pyrroles and N-arylacrylamides with(hetero)aryl halides, respectively, leading to the formation of two sets of structurally important scaffolds including pyrrole-containing biaryls and 3,3-disubstituted oxindoles with high selectivity. We anticipate this study will not only unveil the new potential of IVPs, but also offer a distinct type of catalysts for organic transformations.
