Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment  

作　　者：Amania A.Sheikh Joanna R.Groom 

机构地区：[1]Divisions of Immunology and Molecular Immunology,Walter and Eliza Hall Institute of Medical Research,Parkville,VIC 3052,Australia [2]Department of Medical Biology,University of Melbourne,Parkville,VIC 3010,Australia

出　　处：《Cellular & Molecular Immunology》2021年第3期528-538,共11页中国免疫学杂志（英文版）

基　　金：supported by National Health and Medical Research Council(NHMRC)grants to J.R.G.,an Ideas Grant(GNT1182649)and a Project Grant(GNT1137989);supported by a University of Melbourne research scholarship;supported by an Australian Research Council Future Fellowship(FT130100708).

摘　　要：During viral infection,immune cells coordinate the induction of inflammatory responses that clear infection and humoral responses that promote protection.CD4^(+)T-cell differentiation sits at the center of this axis.Differentiation toward T-helper 1(Th1)cells mediates inflammation and pathogen clearance,while T follicular helper(Tfh)cells facilitate germinal center(GC)reactions for the generation of high-affinity antibodies and immune memory.While Th1 and Tfh differentiation occurs in parallel,these CD4^(+)T-cell identities are mutually exclusive,and progression toward these ends is determined via the upregulation of T-bet and Bcl6,respectively.These lineage-defining transcription factors act in concert with multiple networks of transcriptional regulators that tip the T-bet and Bd6 axis in CD4^(+)T-cell progenitors to either a Th1 or Tfh fate.It is now clear that these transcriptional networks are guided by cytokine cues that are not only varied between distinct viral infections but also dynamically altered throughout the duration of infection.Thus,multiple intrinsic and extrinsic factors combine to specify the fate,plasticity,and function of Th1 and Tfh cells during infection.Here,we review the current information on the mode of action of the lineage-defining transcription factors Bcl6 and T-bet and how they act individually and in complex to govern CD4^(+)T-cell ontogeny.Furthermore,we outline the multifaceted transcriptional regulatory networks that act upstream and downstream of Bcl6 and T-bet to tip the differentiation equilibrium toward either a Tfh or Th1 fate and how these are impacted by dynamic inflammatory cues.

关 键 词：CYTOKINES Infection T follicular helper cells T-helper 1 cells Transcription factors 

分 类 号：R392[医药卫生—免疫学]