Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innat...Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innate and adaptive immune responses. To date, 10 functional TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13)[1]. TLRs are evolutionarily conserved type I transmembrane proteins and comprise an ectodomain characterized by leucine-rich repeats mediating the recognition of ligands, a transmembrane region, and cytosolic Toll-interleukin (IL)-1 receptor domains that activate the downstream signaling pathways [1].展开更多
Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root...Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain.Here,we show that TLR8 was persistently increased in the trigeminal ganglion(TG)neurons in model of TNP induced by partial infraorbital nerve ligation(pIONL).In addition,deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia,reduced the activation of ERK and p38-MAPK,and decreased the expression of pro-inflammatory cytokines in the TG.Furthermore,intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity.VTX-2337 also increased the intracellular Ca^(2+)concentration,induced the activation of ERK and p38,and increased the expression of pro-inflammatory cytokines in the TG.These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation.Targeting TLR8 signaling may be effective for the treatment of TNP.展开更多
Correction to“METTL5 promotes cell proliferation,invasion,and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer”in World J Gastrointest Oncol 2024;16(5):2006-2017,published by Kong LS,T...Correction to“METTL5 promotes cell proliferation,invasion,and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer”in World J Gastrointest Oncol 2024;16(5):2006-2017,published by Kong LS,Tao R,Li YF,Wang WB,and Zhao X.In this article,we added the correct images.展开更多
The endosomal Toll-like receptors （TLRs） TLR3, TLR7, TLR8 and TLR9 are important in sensing foreign nucleic acids encountered by phagocytes. Because TLR8 was initially thought to be non-functional in mice, less is k...The endosomal Toll-like receptors （TLRs） TLR3, TLR7, TLR8 and TLR9 are important in sensing foreign nucleic acids encountered by phagocytes. Because TLR8 was initially thought to be non-functional in mice, less is known about TLR8 than the genetically and functionally related TLR7. Originally associated with the recognition of single-stranded RNA of viral origin, there is now evidence that human TLR8 is also able to sense bacterial RNA released within phagosomal vacuoles, inducing the production of both nuclear factor （NF）-κB-dependent cytokines and type I interferons （IFNs）, such as IFN-β. The functions of TLR8 extend beyond the recognition of foreign pathogens and include cross-talk with other endosomal TLRs, a process that may also have a role in the generation of autoimmunity.展开更多
Toll-like receptors(TLRs)play important roles in immune responses against pathogens and tumors.Recently,TLR8 has gained attention because of its association with multiple inflammatory diseases,infections and antitumor...Toll-like receptors(TLRs)play important roles in immune responses against pathogens and tumors.Recently,TLR8 has gained attention because of its association with multiple inflammatory diseases,infections and antitumor responses.TLR8 senses the degradation products of single-stranded RNA from microbes and self-released RNA to induce type I interferons,inflammatory gene expression and nucleotide-binding and oligomerization domain–,leucine-rich repeat–and pyrin domain–containing protein 3(NLRP3)inflammasome activation.So far,the understanding of TLR8 function in vivo is still limited,partially because of lacking a reliable rodent animal model.Murine Tlr8 cannot sense the ligands of human TLR8.In mammals,TLR8 distinguishes live bacteria from dead bacteria to regulate the magnitude of immune responses.Recently,TLR8 has been reported to recognize severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)RNA to induce inflammatory responses,suggesting that TLR8 participates in coronavirus disease 2019(COVID-19).In this review,we discuss the mechanism of ligand recognition by TLR8,TLR8-mediated signaling pathways and signaling crosstalk between TLR8 and other molecules,and untangle the contribution of TLR8 to inflammatory diseases,infectious diseases,antitumor immunity and vaccination.展开更多
基金supported by grants from the National Natural Science Foundation of China (81870874, 31371179, and 81300968)the Natural Science Foundation of Jiangsu Province, China (BK20170004 and 2015-JY-029)
文摘Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innate and adaptive immune responses. To date, 10 functional TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13)[1]. TLRs are evolutionarily conserved type I transmembrane proteins and comprise an ectodomain characterized by leucine-rich repeats mediating the recognition of ligands, a transmembrane region, and cytosolic Toll-interleukin (IL)-1 receptor domains that activate the downstream signaling pathways [1].
基金the National Natural Science Foundation of China(31970938,31671091,31871064,81571070,and 31700899)the Natural Science Research Program of Jiangsu Province,China(BK20171255 and BK20191448)+1 种基金the Qing Lan Projectthe Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province,China(201810304029Z)。
文摘Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain.Here,we show that TLR8 was persistently increased in the trigeminal ganglion(TG)neurons in model of TNP induced by partial infraorbital nerve ligation(pIONL).In addition,deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia,reduced the activation of ERK and p38-MAPK,and decreased the expression of pro-inflammatory cytokines in the TG.Furthermore,intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity.VTX-2337 also increased the intracellular Ca^(2+)concentration,induced the activation of ERK and p38,and increased the expression of pro-inflammatory cytokines in the TG.These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation.Targeting TLR8 signaling may be effective for the treatment of TNP.
文摘Correction to“METTL5 promotes cell proliferation,invasion,and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer”in World J Gastrointest Oncol 2024;16(5):2006-2017,published by Kong LS,Tao R,Li YF,Wang WB,and Zhao X.In this article,we added the correct images.
文摘The endosomal Toll-like receptors （TLRs） TLR3, TLR7, TLR8 and TLR9 are important in sensing foreign nucleic acids encountered by phagocytes. Because TLR8 was initially thought to be non-functional in mice, less is known about TLR8 than the genetically and functionally related TLR7. Originally associated with the recognition of single-stranded RNA of viral origin, there is now evidence that human TLR8 is also able to sense bacterial RNA released within phagosomal vacuoles, inducing the production of both nuclear factor （NF）-κB-dependent cytokines and type I interferons （IFNs）, such as IFN-β. The functions of TLR8 extend beyond the recognition of foreign pathogens and include cross-talk with other endosomal TLRs, a process that may also have a role in the generation of autoimmunity.
文摘Toll-like receptors(TLRs)play important roles in immune responses against pathogens and tumors.Recently,TLR8 has gained attention because of its association with multiple inflammatory diseases,infections and antitumor responses.TLR8 senses the degradation products of single-stranded RNA from microbes and self-released RNA to induce type I interferons,inflammatory gene expression and nucleotide-binding and oligomerization domain–,leucine-rich repeat–and pyrin domain–containing protein 3(NLRP3)inflammasome activation.So far,the understanding of TLR8 function in vivo is still limited,partially because of lacking a reliable rodent animal model.Murine Tlr8 cannot sense the ligands of human TLR8.In mammals,TLR8 distinguishes live bacteria from dead bacteria to regulate the magnitude of immune responses.Recently,TLR8 has been reported to recognize severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)RNA to induce inflammatory responses,suggesting that TLR8 participates in coronavirus disease 2019(COVID-19).In this review,we discuss the mechanism of ligand recognition by TLR8,TLR8-mediated signaling pathways and signaling crosstalk between TLR8 and other molecules,and untangle the contribution of TLR8 to inflammatory diseases,infectious diseases,antitumor immunity and vaccination.
