Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of acti...Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.展开更多
Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current...Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.展开更多
Innate lymphoid cells(ILCs),a newly identified member of the lymphoid population,play a critical role in the transition from innate to adaptive immunity in host defense.ILCs are important in mucosal barrier immunity,t...Innate lymphoid cells(ILCs),a newly identified member of the lymphoid population,play a critical role in the transition from innate to adaptive immunity in host defense.ILCs are important in mucosal barrier immunity,tissue homeostasis,and immune regulation throughout the body.Significant alterations in ILC responses in lung diseases have been observed and reported.Emerging evidence has shown that ILCs are importantly involved in the pathogenesis and development of a variety of lung diseases,i.e.,helminth infections,allergic airway inflammation,and airway hyper-responsiveness.However,as a tissue-resident cell population,the role of ILCs in the lung remains poorly characterized.In this review,we discuss the role of ILCs in lung diseases,the mechanisms underlying the ILCmediated regulation of immunity,and the therapeutic potential of modulating ILC responses.展开更多
Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understo...Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.展开更多
The incidence of sepsis is increasing over time, along with an increased risk of dying from the condition. Sepsis care costs billions annually in the United States. Death from sepsis is understood to be a complex proc...The incidence of sepsis is increasing over time, along with an increased risk of dying from the condition. Sepsis care costs billions annually in the United States. Death from sepsis is understood to be a complex process, driven by a lack of normal immune homeostatic functions and excessive production of proinflammatory cytokines, which leads to multi-organ failure. The Toll-like receptor(TLR) family, one of whose members was initially discovered in Drosophila, performs an important role in the recognition of microbial pathogens. These pattern recognition receptors(PRRs), upon sensing invading microorganisms, activate intracellular signal transduction pathways. NOD signaling is also involved in the recognition of bacteria and acts synergistically with the TLR family in initiating an efficient immune response for the eradication of invading microbial pathogens. TLRs and NOD1/NOD2 respond to different pathogenassociated molecular patterns(PAMPs). Modulation of both TLR and NOD signaling is an area of research that has prompted much excitement and debate as a therapeutic strategy in the management of sepsis. Molecules targeting TLR and NOD signaling pathways exist but regrettably thus far none have proven efficacy from clinical trials.展开更多
Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipo...Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB （NF-κB） activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.展开更多
Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During ma...Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.展开更多
This paper is to further understand how APOBEC3G can defend the retroviruses and to find new approaches to AIDs （acquired immure deficiency syndrome）.The viral infectivity factor （Vif） induces rapid degradation of...This paper is to further understand how APOBEC3G can defend the retroviruses and to find new approaches to AIDs （acquired immure deficiency syndrome）.The viral infectivity factor （Vif） induces rapid degradation of APOBEC3G by ubiquitination, which is a proteosome-dependent pathway. Precisely speaking, only in the virus-producing cell Vif expression is necessary; in its absence, infection of a subsequent target cell terminates at a postentry step through the action of the human APOBEC3G antiviral mechanism. Hf protein has two domains： one binds to APOBEC3G and the other regulates the degradation of APOBEC3G by a conserved sequence, SLQ （Y/F） LA motif. Recently, the research on Vif has also revealed APOBEC3G is a novel component of innate immune system. In fact, APOBEC3G not only acts in DNA editing to block the replication of retroviruses such as HIV-1, but also is able to defend a wide spectrum of distantly related retroviruses and interferes with HBV through a different mechanism from HIE.展开更多
基金supported by College Student Innovation and Entrepreneurship Training(202110069122)Tianjin Key R&D Plan-Key Projects Supported by Science and Technology(19YFZCSN00010)Tianjin Agricultural Science and Technology Achievements Transformation and Promotion Project(202101120)。
文摘Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.
基金National Key R&D Program of China(2019YFA0110600)National Natural Science Foundation of China(81970916,81671031)the LU JIAXI International team program supported by the K.C.Wong Education Foundation and CAS and the Youth Innovation Promotion Association of CAS(Grant No.2016236).
文摘Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.
基金supported by the USA National Institutes of Health Grant R01-HL-079669(J.F.)USA National Institutes of Health Grant R01-HL076179(J.F.)+2 种基金USA National Institutes of Health Grant R56-HL-123882(J.F.)USA VA Merit Award 1I01BX002729(J.F.)the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents(Q.S.)
文摘Innate lymphoid cells(ILCs),a newly identified member of the lymphoid population,play a critical role in the transition from innate to adaptive immunity in host defense.ILCs are important in mucosal barrier immunity,tissue homeostasis,and immune regulation throughout the body.Significant alterations in ILC responses in lung diseases have been observed and reported.Emerging evidence has shown that ILCs are importantly involved in the pathogenesis and development of a variety of lung diseases,i.e.,helminth infections,allergic airway inflammation,and airway hyper-responsiveness.However,as a tissue-resident cell population,the role of ILCs in the lung remains poorly characterized.In this review,we discuss the role of ILCs in lung diseases,the mechanisms underlying the ILCmediated regulation of immunity,and the therapeutic potential of modulating ILC responses.
基金supported by grants from the National Center of Complementary and Alternative Medicine (NCCAM, R01AT005076)the National Institute of General Medical Sciences (NIGMS, R01GM063075)
文摘Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.
基金supported by the National Natural Science Foundation of China (Grant 81420108022)Jiangsu Province Program of Innovative and Entrepreneurial Talents (2011 – 2014)
文摘The incidence of sepsis is increasing over time, along with an increased risk of dying from the condition. Sepsis care costs billions annually in the United States. Death from sepsis is understood to be a complex process, driven by a lack of normal immune homeostatic functions and excessive production of proinflammatory cytokines, which leads to multi-organ failure. The Toll-like receptor(TLR) family, one of whose members was initially discovered in Drosophila, performs an important role in the recognition of microbial pathogens. These pattern recognition receptors(PRRs), upon sensing invading microorganisms, activate intracellular signal transduction pathways. NOD signaling is also involved in the recognition of bacteria and acts synergistically with the TLR family in initiating an efficient immune response for the eradication of invading microbial pathogens. TLRs and NOD1/NOD2 respond to different pathogenassociated molecular patterns(PAMPs). Modulation of both TLR and NOD signaling is an area of research that has prompted much excitement and debate as a therapeutic strategy in the management of sepsis. Molecules targeting TLR and NOD signaling pathways exist but regrettably thus far none have proven efficacy from clinical trials.
基金Supported by the Grant from the Educational Department of Liaoning Province(2008810)
文摘Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB （NF-κB） activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.
文摘Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.
基金the Cultivating Funds of Academic and Technical Leaders in Sichuan Province (No. 2200338)
文摘This paper is to further understand how APOBEC3G can defend the retroviruses and to find new approaches to AIDs （acquired immure deficiency syndrome）.The viral infectivity factor （Vif） induces rapid degradation of APOBEC3G by ubiquitination, which is a proteosome-dependent pathway. Precisely speaking, only in the virus-producing cell Vif expression is necessary; in its absence, infection of a subsequent target cell terminates at a postentry step through the action of the human APOBEC3G antiviral mechanism. Hf protein has two domains： one binds to APOBEC3G and the other regulates the degradation of APOBEC3G by a conserved sequence, SLQ （Y/F） LA motif. Recently, the research on Vif has also revealed APOBEC3G is a novel component of innate immune system. In fact, APOBEC3G not only acts in DNA editing to block the replication of retroviruses such as HIV-1, but also is able to defend a wide spectrum of distantly related retroviruses and interferes with HBV through a different mechanism from HIE.
