By creating an immune checkpoint blockade-induced colitis model,Lo et al.(2024)have suggested a strategy for alleviating gastrointestinal immune-related adverse events while preserving the antitumor stimulatory effect...By creating an immune checkpoint blockade-induced colitis model,Lo et al.(2024)have suggested a strategy for alleviating gastrointestinal immune-related adverse events while preserving the antitumor stimulatory effects of CTLA-4 blockade within this microbiota-dependent model.展开更多
Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021...Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021 by the Food and Drug Administration(FDA)in the US.The launch of Saphnelo marked the only new treatment approved for systemic lupus erythematosus(SLE)in more than 10 years.展开更多
We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regi...We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.展开更多
Kidney is a major target organ in both antiphospholipid syndrome(APS)and systemic lupus erythematosus(SLE).The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis(APSN-LN)is intricate and rema...Kidney is a major target organ in both antiphospholipid syndrome(APS)and systemic lupus erythematosus(SLE).The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis(APSN-LN)is intricate and remains largely unrevealed.We proposed in present work,that generation of antiphospholipid antibodies(aPLs),especially those directed towards the oxidized neoepitopes,are largely linked with the redox status along with disease progression.Moreover,we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN.SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties.In current study,we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice,a murine model develops syndrome resembled human APS associated with SLE,for the first time.SM934 treatment comprehensively impeded autoantibodies production,inflammatory cytokine accumulation and excessive oxidative stress in kidney.Among others,we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets.Collectively,our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.展开更多
Cytokines are small cell-signaling proteins which are critical coordinators for the immune response that takes place in infection and inflammation.A recent study published in Cell by Yen et al.1 demonstrated an innova...Cytokines are small cell-signaling proteins which are critical coordinators for the immune response that takes place in infection and inflammation.A recent study published in Cell by Yen et al.1 demonstrated an innovative modular platform enabled engineering surrogate ligand for cytokine receptors therein displayed versatile functional activities.Further,the novel“cytokine med-chem”strategy they presented has been proved to be applicable to many cell surface transmembrane receptor systems,especially for the surrogate interferons(IFNs),that exhibited potent inhibition of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with restrained proinflammatory effects.This research provided a powerful screening platform for cytokine drug discovery and particularly inspired the development of small molecule drugs for Corona virus disease-2019(COVID-19).展开更多
基金supported by the National Natural Science Foundation of China(82374108)Shanghai Municipal Science and Technology Major Project(TM202301D003)。
文摘By creating an immune checkpoint blockade-induced colitis model,Lo et al.(2024)have suggested a strategy for alleviating gastrointestinal immune-related adverse events while preserving the antitumor stimulatory effects of CTLA-4 blockade within this microbiota-dependent model.
基金the National Natural Science Foundation of China(Grant Number:81903882,81871240,82001709)the Science and Technology Commission of Shanghai Municipality(Grant Number:22ZR1473700,21S11907700)"Science and Technology Innovation Action Plan"medicine innovation fund by Science and Technology Commission of Shanghai Municipality(Grant Number:21Y31900200).
文摘Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021 by the Food and Drug Administration(FDA)in the US.The launch of Saphnelo marked the only new treatment approved for systemic lupus erythematosus(SLE)in more than 10 years.
文摘We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.
基金supported by the National Natural Science Foundation of China(81903882 and 81871240)the National Science and Technology Major Project“New Drug Creation and Manufacturing Program”(2018ZX09711002-014-001)the Personalized Medicines——“Molecular Signature-based Drug Discovery and Development”,Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12020107 and XDA12020369).
文摘Kidney is a major target organ in both antiphospholipid syndrome(APS)and systemic lupus erythematosus(SLE).The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis(APSN-LN)is intricate and remains largely unrevealed.We proposed in present work,that generation of antiphospholipid antibodies(aPLs),especially those directed towards the oxidized neoepitopes,are largely linked with the redox status along with disease progression.Moreover,we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN.SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties.In current study,we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice,a murine model develops syndrome resembled human APS associated with SLE,for the first time.SM934 treatment comprehensively impeded autoantibodies production,inflammatory cytokine accumulation and excessive oxidative stress in kidney.Among others,we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets.Collectively,our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.
基金supported by the Science and Technology Commission of Shanghai Municipality Natural Science Foundation Project[grant numbers:22ZR1473700].
文摘Cytokines are small cell-signaling proteins which are critical coordinators for the immune response that takes place in infection and inflammation.A recent study published in Cell by Yen et al.1 demonstrated an innovative modular platform enabled engineering surrogate ligand for cytokine receptors therein displayed versatile functional activities.Further,the novel“cytokine med-chem”strategy they presented has been proved to be applicable to many cell surface transmembrane receptor systems,especially for the surrogate interferons(IFNs),that exhibited potent inhibition of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with restrained proinflammatory effects.This research provided a powerful screening platform for cytokine drug discovery and particularly inspired the development of small molecule drugs for Corona virus disease-2019(COVID-19).
