Powdery mildew(PM),caused by the biotrophic fungus Podospharea leucotricha,poses a significant threat to apple production.Salicylic acid(SA)signaling plays a crucial role in enhancing resistance to biotrophic pathogen...Powdery mildew(PM),caused by the biotrophic fungus Podospharea leucotricha,poses a significant threat to apple production.Salicylic acid(SA)signaling plays a crucial role in enhancing resistance to biotrophic pathogens.While PR1,a defense protein induced by SA,is essential for plant immunity,its excessive accumulation can be detrimental.However,the mechanism of PR1-mediated immune balance remains unclear.This study identified a key transcription factor,WRKY1,which enhances the SA accumulation by modulating the SA biosynthesis gene EPS1,while simultaneously regulating the WRKY40-NPR3g module to prevent sustained PR1 expression caused by continuous SA accumulation.Specifically,the transcription factor WRKY40 upregulates NPR3g expression,and NPR3g interacts with NPR1 in an SA-dependent manner.Then,two TGA2c variants that interact with NPR1 to activate PR1 expression were identified:canonical TGA2c-1 and alternative splicing of TGA2c-2 with an exon deletion.SA does not influence the NPR1-TGA2c-1 interaction but is essential for the NPR1-TGA2c-2 interaction.Notably,NPR3g reduces PR1 levels by selectively disrupting the NPR1-TGA2c-2 complex through competition for the BTB-POZ domain of NPR1.In conclusion,this study identifies a novel mechanism by which WRKY1 modulates PR1-mediated immune balance to defend against PM.展开更多
The early life period is a critical phase for the colonization of initial gut microbes in infants,during which the immune system develops and matures.These processes have long-lasting implications that may extend into...The early life period is a critical phase for the colonization of initial gut microbes in infants,during which the immune system develops and matures.These processes have long-lasting implications that may extend into adolescence and even adulthood.Bifidobacterium longum subsp.infantis,recognized as an ideal probiotic during infancy,has the potential to modulate intestinal immunity and mitigate immune-mediated diseases.This research explored the potential of various B.longum subsp.infantis strains to modulate the balance between T helper(Th)1 and Th2 responses,immune cell populations,Immunoglobulin A(IgA),and the related genes expression in mice.Notably,B.longum subsp.infantis FHNFQ4M11 and CCFM1269 demonstrated more robust regulatory capabilities.These two strains,which exhibited higher ILA production,activated the aryl hydrocarbon receptor(AHR)signaling pathway,upregulated the levels of galectin-1(Gal-1)and galectin-3(Gal-3),and modulated Th1/Th2 differentiation markers in the colon.Additionally,these strains significantly elevated IgA concentrations in both serum and colon and modulated the gut microbiota composition.These findings underscored the potential of specific B.longum subsp.infantis strains as targeted probiotic interventions in early life,providing a promising strategy for promoting immune homeostasis and gut health in infants.展开更多
Tumorigenesis are closely associated with the immune function of the human body.Immunotherapy has emerged as a novel and promising treatment strategy in multiple malignancies in the 21st century.Traditional Chinese me...Tumorigenesis are closely associated with the immune function of the human body.Immunotherapy has emerged as a novel and promising treatment strategy in multiple malignancies in the 21st century.Traditional Chinese medicine(TCM)has been extensively used for cancer treatment in China and surrounding countries for it exerts efficient therapeutic effects with few side effects.In recent years,studies have demonstrated that TCM plays a unique and reliable role in regulating tumor immunity.TCM can enhance the antitumor immune response function by regulating the secretion of cytokines,reshaping the balance of immune cells,and regulating immune checkpoints to relieve the immunosuppression.In addition,TCM can reduce the side effects(e.g.,cytokine storm)of cancer immunotherapy.Based on the current research of active immunotherapy and passive immunotherapy,this review summarizes the potential applications and existing problems of TCM in tumor immunotherapy.This review may be helpful in illuminating the scientific basis of TCM in tumor immunotherapy,promoting its internationalization,as well as shedding innovating new strategies for the development of tumor immunotherapy.展开更多
Objective To study the therapeutic effects of Sophora flavescens on T helper 1 cell/T helper 2 cell(Th1/Th2)imbalance in atopic dermatitis(AD)and its potential mechanismM.I ethods Totally 24 female C57BL/6 mice were r...Objective To study the therapeutic effects of Sophora flavescens on T helper 1 cell/T helper 2 cell(Th1/Th2)imbalance in atopic dermatitis(AD)and its potential mechanismM.I ethods Totally 24 female C57BL/6 mice were randomly divided into normal control group,AD group,and AD+Sophora flavescens group by stratified body weight,8 mice in each group.AD mouse mode1l was induced by 2,4-dinitrochlorobenzene/Dermatophagoides farinae extract(DNCB/DFE).HaCaT were divided into three groups:control group,interferon-γ(IFN-γ)/tumor necrosis factor-α(TNF-α)group,and IFN-γ/TNF-α+Sophora flavescens group.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expressions of IFN-γ,TNF-α,interleukin-2(IL-2),thymus activation-regulated chemokine(TARC),IL-4,IL-5,and IL-6.The protein expressions of phospho-mitogen activated protein kinase p38(p-p38),p38,phospho-nuclear factor kappa B p65 subunit(p-p65)and p65 in tissues and cells were detected by Western Blot.ELISA was used to detect the release levels of IL-6 and TARC,and the ratio of Th1/Th2 cells in flow cytometry.Results Compared with the control group,IL-6 and TARC mRNA and protein expressions significantly increased(P<0.01),and expressions of p-p38 and p-p65 proteins were upregulated(P<0.01)in IFN-γ/TNF-α group.Compared with the IFN-γ/TNF-αgroup,IL-6 and TARC mRNA and protein expressions significantly decreased(P<0.01),and the protein expressions of p-p38 and p-p65 were significantly down-regulated(P<0.01)in the IFN-γ/TNF-α+Sophora flavescens group.At the animal level,compared with the normal control group,the expression levels of p-p38 and p-p65 protein in the skin tissue significantlyyincreased(P<0.01),infiltrationof inflammatory cells increased in the ear skin tissue,hyperkeratinization and infiltration of mast cells also increased(P<0.05),and Th2 cells increased in the skin(P<0.01),expressions of IFN-γ,TNF-α,TARC,IL-6,IL4,and IL-5 in mouse skin increased(P<0.01)in the AD model group.Compared with the AD model group,after Sophora flavescens intervention,the expression levels of p-p38 and p-p65 protein decreased in the skin tissue of mice in AD+Sophora flavescens treatment group(P<0.01).The thickness of epidermis and dermis and the number of mast cells were significantly lowered(P<0.05).The amount of Th2 cells and the expression levels of TARC,IL-6,IL-4,and IL-5 in mouse tissues significantly decreased in AD+Sophora flavescens treatment group(P<0.01).Conclusion Sophora flavescens alleviate symptoms of AD possibly by improving the imbalance of Th1/Th2 and inhibiting MAPK/NF-kB signaling pathways.展开更多
The ubiquitin-proteasome system(UPS) serves as a highly complicated yet conserved pathway that plays a pivotal role in plant growth and development,stress responses,and defense against pathogens.UPS operates through a...The ubiquitin-proteasome system(UPS) serves as a highly complicated yet conserved pathway that plays a pivotal role in plant growth and development,stress responses,and defense against pathogens.UPS operates through a cascade of enzymatic reactions.The ubiquitin-activating enzyme(E1) activates ubiquitin in an ATP-dependent manner,which is then transferred to the ubiquitin-conjugating enzyme(E2).展开更多
Immune imbalance is a critical factor in the occurrence and progression of cancers because it disrupts the immune system's ability to detect and eliminate abnormal cells.Restoring immune balance and reactivating i...Immune imbalance is a critical factor in the occurrence and progression of cancers because it disrupts the immune system's ability to detect and eliminate abnormal cells.Restoring immune balance and reactivating immune cells remain major challenges in cancer immunotherapy.Current immunoregulatory strategies,such as immune checkpoint blockade,adoptive cell therapy,and therapeutic vaccines,aim to influence key immune cells,such as T cells,dendritic cells,and macrophages,to boost anticancer responses.However,conventional material design in immunotherapy usually emphasizes chemical composition and physical morphology,while neglecting the critical role of stereochemistry in immune cell recognition and activation.展开更多
ROOT IMMUNOMETABOLISM:BALANCING DEFENSE AND ACCOMMODATION.Plant health depends on balanced immune defense and microbial accommodation.As constant contact zones,roots must exclude pathogens while fostering beneficial s...ROOT IMMUNOMETABOLISM:BALANCING DEFENSE AND ACCOMMODATION.Plant health depends on balanced immune defense and microbial accommodation.As constant contact zones,roots must exclude pathogens while fostering beneficial symbionts.Classical,leafbased immunity models fail to capture the spatial and metabolic complexity of roots,which contain functionally distinct zones and cell types with diverse immune sensitivities and responses(Tsai et al.,2023).展开更多
基金This research was supported by the National Natural Science Foundation of China(NSFC)through grant numbers 31171935 and 31560551.
文摘Powdery mildew(PM),caused by the biotrophic fungus Podospharea leucotricha,poses a significant threat to apple production.Salicylic acid(SA)signaling plays a crucial role in enhancing resistance to biotrophic pathogens.While PR1,a defense protein induced by SA,is essential for plant immunity,its excessive accumulation can be detrimental.However,the mechanism of PR1-mediated immune balance remains unclear.This study identified a key transcription factor,WRKY1,which enhances the SA accumulation by modulating the SA biosynthesis gene EPS1,while simultaneously regulating the WRKY40-NPR3g module to prevent sustained PR1 expression caused by continuous SA accumulation.Specifically,the transcription factor WRKY40 upregulates NPR3g expression,and NPR3g interacts with NPR1 in an SA-dependent manner.Then,two TGA2c variants that interact with NPR1 to activate PR1 expression were identified:canonical TGA2c-1 and alternative splicing of TGA2c-2 with an exon deletion.SA does not influence the NPR1-TGA2c-1 interaction but is essential for the NPR1-TGA2c-2 interaction.Notably,NPR3g reduces PR1 levels by selectively disrupting the NPR1-TGA2c-2 complex through competition for the BTB-POZ domain of NPR1.In conclusion,this study identifies a novel mechanism by which WRKY1 modulates PR1-mediated immune balance to defend against PM.
基金supported by the National Natural Science Foundation of China(32394051)the Fundamental Research Funds for the Central Universitiesthe Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province.
文摘The early life period is a critical phase for the colonization of initial gut microbes in infants,during which the immune system develops and matures.These processes have long-lasting implications that may extend into adolescence and even adulthood.Bifidobacterium longum subsp.infantis,recognized as an ideal probiotic during infancy,has the potential to modulate intestinal immunity and mitigate immune-mediated diseases.This research explored the potential of various B.longum subsp.infantis strains to modulate the balance between T helper(Th)1 and Th2 responses,immune cell populations,Immunoglobulin A(IgA),and the related genes expression in mice.Notably,B.longum subsp.infantis FHNFQ4M11 and CCFM1269 demonstrated more robust regulatory capabilities.These two strains,which exhibited higher ILA production,activated the aryl hydrocarbon receptor(AHR)signaling pathway,upregulated the levels of galectin-1(Gal-1)and galectin-3(Gal-3),and modulated Th1/Th2 differentiation markers in the colon.Additionally,these strains significantly elevated IgA concentrations in both serum and colon and modulated the gut microbiota composition.These findings underscored the potential of specific B.longum subsp.infantis strains as targeted probiotic interventions in early life,providing a promising strategy for promoting immune homeostasis and gut health in infants.
基金supported by the National Natural Science Foundation of China(82074165,81873306,81973526,81703749,81703764)Guangdong Science and Technology Department(2016A030306025)+7 种基金Guangdong High-level Personnel of Special Support Program(A1-3002-16-111-003)Department of Education of Guangdong Province(2018KZDXM022,A1-2606-19-111-009)the Ph.D.Start-up Fund of Natural Science Foundation of Guangdong Province(2017A030310213)Science and Technology Planning Project of Guangdong Province(2017B030314166)Guangzhou science and technology project(201904010407)the Specific Research Fund for TCM Science and Technology of Guangdong provincial Hospital of Chinese Medicine(YN2018MJ07)and the Foundation for Young Scholars of Guangzhou University of Chinese Medicine(QNYC20190101)Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research(2020B1212030006).
文摘Tumorigenesis are closely associated with the immune function of the human body.Immunotherapy has emerged as a novel and promising treatment strategy in multiple malignancies in the 21st century.Traditional Chinese medicine(TCM)has been extensively used for cancer treatment in China and surrounding countries for it exerts efficient therapeutic effects with few side effects.In recent years,studies have demonstrated that TCM plays a unique and reliable role in regulating tumor immunity.TCM can enhance the antitumor immune response function by regulating the secretion of cytokines,reshaping the balance of immune cells,and regulating immune checkpoints to relieve the immunosuppression.In addition,TCM can reduce the side effects(e.g.,cytokine storm)of cancer immunotherapy.Based on the current research of active immunotherapy and passive immunotherapy,this review summarizes the potential applications and existing problems of TCM in tumor immunotherapy.This review may be helpful in illuminating the scientific basis of TCM in tumor immunotherapy,promoting its internationalization,as well as shedding innovating new strategies for the development of tumor immunotherapy.
文摘Objective To study the therapeutic effects of Sophora flavescens on T helper 1 cell/T helper 2 cell(Th1/Th2)imbalance in atopic dermatitis(AD)and its potential mechanismM.I ethods Totally 24 female C57BL/6 mice were randomly divided into normal control group,AD group,and AD+Sophora flavescens group by stratified body weight,8 mice in each group.AD mouse mode1l was induced by 2,4-dinitrochlorobenzene/Dermatophagoides farinae extract(DNCB/DFE).HaCaT were divided into three groups:control group,interferon-γ(IFN-γ)/tumor necrosis factor-α(TNF-α)group,and IFN-γ/TNF-α+Sophora flavescens group.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expressions of IFN-γ,TNF-α,interleukin-2(IL-2),thymus activation-regulated chemokine(TARC),IL-4,IL-5,and IL-6.The protein expressions of phospho-mitogen activated protein kinase p38(p-p38),p38,phospho-nuclear factor kappa B p65 subunit(p-p65)and p65 in tissues and cells were detected by Western Blot.ELISA was used to detect the release levels of IL-6 and TARC,and the ratio of Th1/Th2 cells in flow cytometry.Results Compared with the control group,IL-6 and TARC mRNA and protein expressions significantly increased(P<0.01),and expressions of p-p38 and p-p65 proteins were upregulated(P<0.01)in IFN-γ/TNF-α group.Compared with the IFN-γ/TNF-αgroup,IL-6 and TARC mRNA and protein expressions significantly decreased(P<0.01),and the protein expressions of p-p38 and p-p65 were significantly down-regulated(P<0.01)in the IFN-γ/TNF-α+Sophora flavescens group.At the animal level,compared with the normal control group,the expression levels of p-p38 and p-p65 protein in the skin tissue significantlyyincreased(P<0.01),infiltrationof inflammatory cells increased in the ear skin tissue,hyperkeratinization and infiltration of mast cells also increased(P<0.05),and Th2 cells increased in the skin(P<0.01),expressions of IFN-γ,TNF-α,TARC,IL-6,IL4,and IL-5 in mouse skin increased(P<0.01)in the AD model group.Compared with the AD model group,after Sophora flavescens intervention,the expression levels of p-p38 and p-p65 protein decreased in the skin tissue of mice in AD+Sophora flavescens treatment group(P<0.01).The thickness of epidermis and dermis and the number of mast cells were significantly lowered(P<0.05).The amount of Th2 cells and the expression levels of TARC,IL-6,IL-4,and IL-5 in mouse tissues significantly decreased in AD+Sophora flavescens treatment group(P<0.01).Conclusion Sophora flavescens alleviate symptoms of AD possibly by improving the imbalance of Th1/Th2 and inhibiting MAPK/NF-kB signaling pathways.
基金supported by the National Key Research and Development Program of China (2023YFC2604500,2024YFD1200600)the National Natural Science Foundation of China (32472566)。
文摘The ubiquitin-proteasome system(UPS) serves as a highly complicated yet conserved pathway that plays a pivotal role in plant growth and development,stress responses,and defense against pathogens.UPS operates through a cascade of enzymatic reactions.The ubiquitin-activating enzyme(E1) activates ubiquitin in an ATP-dependent manner,which is then transferred to the ubiquitin-conjugating enzyme(E2).
基金financially supported by the National Natural Science Foundation of China(Grant Nos.U23A20591,52273158,52273159,and W2421115)the Science and Technology Department Project of Jilin Province(Grant No.20250204068YY)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.Y2023066).
文摘Immune imbalance is a critical factor in the occurrence and progression of cancers because it disrupts the immune system's ability to detect and eliminate abnormal cells.Restoring immune balance and reactivating immune cells remain major challenges in cancer immunotherapy.Current immunoregulatory strategies,such as immune checkpoint blockade,adoptive cell therapy,and therapeutic vaccines,aim to influence key immune cells,such as T cells,dendritic cells,and macrophages,to boost anticancer responses.However,conventional material design in immunotherapy usually emphasizes chemical composition and physical morphology,while neglecting the critical role of stereochemistry in immune cell recognition and activation.
基金the funding and collaborative framework provided by the iHEAD initiative PB22-025Afunded by the NRW MKW(Ministry of Culture and Science of the State of North Rhine-Westphalia,Germany),which enables the interdisciplinary exploration of immunometabolism and host-microbe interactions in plant and animal systems.
文摘ROOT IMMUNOMETABOLISM:BALANCING DEFENSE AND ACCOMMODATION.Plant health depends on balanced immune defense and microbial accommodation.As constant contact zones,roots must exclude pathogens while fostering beneficial symbionts.Classical,leafbased immunity models fail to capture the spatial and metabolic complexity of roots,which contain functionally distinct zones and cell types with diverse immune sensitivities and responses(Tsai et al.,2023).
