Nck adaptor proteins modulate differentiation and effector function of T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: antibody production;    cell death;    follicular helper T;    germinal center;    Tfh;   

DOI  :  10.1189/jlb.1HI1114-565R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

UnderstandingthemolecularmechanismsregulatingTcellreactivityisrequiredforsuccessfulreprogrammingofimmuneresponsesinmedicalconditions,characterizedbydysfunctionsoftheimmunesystem.Nckproteinsarecytoplasmicadaptorsmediatingdiversecellularfunctions,includingTCRsignaling.ByenhancingTCRsignalstrength,NckproteinsinfluencethymicselectionandregulatethesizeandsensitivityoftheperipheralTcellrepertoire.Here,weinvestigatedthecontributionofNckproteinstoCD4+TcelldifferentiationandeffectorfunctionusingNck.T−/−mice.ImpairedGCformationandreducedTfhwereobservedinNck.T−/−miceafterimmunizationwithTcell‐dependentantigens.Th2/Tfh‐relatedcytokines,suchasIL‐4,IL‐10,andIL‐21,weredecreasedinNck.T−/−miceTcells.Moreover,anincreasedsusceptibilitytocelldeathofTfhcellsinNck.T−/−micewasassociatedwithdecreasedlevelsofAktphosphorylation.AsaresultofthisdysregulationinTfhcellsofNck.T−/−mice,wefoundimpairedproductionandaffinitymaturationofantibodiesagainstTcell‐dependentantigens.Thus,NckproteinsnotonlyparticipateinthymicselectionandgenerationoftheperipheralTcellrepertoirebutalsoareinvolvedinthedifferentiationandeffectorfunctionsofCD4+Tcells...

【 授权许可】

CC BY