The ever-growing research on lymphatic biology has clearly identified lymphatic vessels as key players that maintain human health through their functional roles in tissue fluid homeostasis,immunosurveillance,lipid met...The ever-growing research on lymphatic biology has clearly identified lymphatic vessels as key players that maintain human health through their functional roles in tissue fluid homeostasis,immunosurveillance,lipid metabolism and inflammation.It is therefore not surprising that the list of human diseases associated with lymphatic malfunctions has grown larger,including issues beyond lymphedema,a pathology traditionally associated with lymphatic drainage insufficiency.Thus,the discovery of factors and pathways that can promote optimal lymphatic functions may offer new therapeutic options.Accumulating evidence indicates that aside from biochemical factors,biomechanical signals also regulate lymphatic vessel expansion and functions postnatally.Here,we review how mechanical forces induced by fluid shear stress affect the behavior and functions of lymphatic vessels and the mechanisms lymphatic vessels employ to sense and transduce these mechanical cues into biological signals.展开更多
CD8^(+)T cells play a central role in antiviral immune responses.Upon infection,naive CD8^(+)T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differe...CD8^(+)T cells play a central role in antiviral immune responses.Upon infection,naive CD8^(+)T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved.Although extensively investigated,the underlying mechanisms of CD+T-cell differentiation remain incompletely understood.Themis is a T-cell-specific protein that plays critical roles in T-cell development.Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8^(+)T-cell homeostasis,cytokine responsiveness,and antibacterial responses.In this study,we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection.We found that preexisting CD8^(+)T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice.Further analyses showed that in the primary immune response,Themis deficiency promoted the differentiation of CD8^(+)effector cells and increased their TNF and IFNy production.Moreover,Themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)differentiation.Themis deficiency also enhanced effector cytokine production in memory CD8^(+)T cells while impairing central memory CD8^(+)T-cell formation.Mechanistically,we found that Themis mediates PD-1 expression and its signaling in effector CD8^(+)T cells,which explains the elevated cytokine production in these cells when Themis is disrupted.展开更多
SARS-CoV-2,as well as the measures that were taken around the world to limit its spread,has killed thousands of people and ruined industries and economies.Vigorous vaccination campaigns are being pursued in the hope o...SARS-CoV-2,as well as the measures that were taken around the world to limit its spread,has killed thousands of people and ruined industries and economies.Vigorous vaccination campaigns are being pursued in the hope of ending the pandemic.However,many people are afraid of vaccination side effects,and one of these suspected side effects is female infertility due to vaccine-induced autoreactive antibodies against Syncytin-1[1].展开更多
基金This work was supported by NUHS internal funding and the Ministry of Education(Project 594 ID:MOE2019-T2-1-136)to VA and the National Medical Research Council(Y-IRG grant)to HYL。
文摘The ever-growing research on lymphatic biology has clearly identified lymphatic vessels as key players that maintain human health through their functional roles in tissue fluid homeostasis,immunosurveillance,lipid metabolism and inflammation.It is therefore not surprising that the list of human diseases associated with lymphatic malfunctions has grown larger,including issues beyond lymphedema,a pathology traditionally associated with lymphatic drainage insufficiency.Thus,the discovery of factors and pathways that can promote optimal lymphatic functions may offer new therapeutic options.Accumulating evidence indicates that aside from biochemical factors,biomechanical signals also regulate lymphatic vessel expansion and functions postnatally.Here,we review how mechanical forces induced by fluid shear stress affect the behavior and functions of lymphatic vessels and the mechanisms lymphatic vessels employ to sense and transduce these mechanical cues into biological signals.
基金the Core Facility of Biomedical Sciences,Xiamen University for Flow Cytometry Cell Sorting service.This study was supported by the National Natural Science Foundation of China(32070887)the Fundamental Research Funds for the Central Universities(20720220003)to G.F.Singapore Ministry of Education(MOE-000112)Singapore Ministry of Health's National Medical Research Council(MOH-000523)to N.RJ.Gascoigne.The Natural Science Foundation of Fujian Province(No.2019J01009)to Q.L.The National Natural Science Foundation of China(U1904206)to X.L.C.The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript。
文摘CD8^(+)T cells play a central role in antiviral immune responses.Upon infection,naive CD8^(+)T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved.Although extensively investigated,the underlying mechanisms of CD+T-cell differentiation remain incompletely understood.Themis is a T-cell-specific protein that plays critical roles in T-cell development.Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8^(+)T-cell homeostasis,cytokine responsiveness,and antibacterial responses.In this study,we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection.We found that preexisting CD8^(+)T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice.Further analyses showed that in the primary immune response,Themis deficiency promoted the differentiation of CD8^(+)effector cells and increased their TNF and IFNy production.Moreover,Themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)differentiation.Themis deficiency also enhanced effector cytokine production in memory CD8^(+)T cells while impairing central memory CD8^(+)T-cell formation.Mechanistically,we found that Themis mediates PD-1 expression and its signaling in effector CD8^(+)T cells,which explains the elevated cytokine production in these cells when Themis is disrupted.
基金This study was funded by the Ministry of Education,Singapore(MOE2019-T2-2-087)Plasma samples were collected in accordance with the Helsinki declaration after written consent from volunteers under an approved Institutional Review Board protocol NUS-IRB REF NO:LH-20-013.
文摘SARS-CoV-2,as well as the measures that were taken around the world to limit its spread,has killed thousands of people and ruined industries and economies.Vigorous vaccination campaigns are being pursued in the hope of ending the pandemic.However,many people are afraid of vaccination side effects,and one of these suspected side effects is female infertility due to vaccine-induced autoreactive antibodies against Syncytin-1[1].
