T helper cell differentiation: on again, off again.
Recent studies raise the possibility that T helper (Th) polarization may be attributable to generalized activation and regulated silencing rather than regulated activation of target cytokine genes. The binding of transcription factors GATA-3 or T-bet to specific enhancers does recruit transcription factors such as NFAT-1 to IL-4 or IFNgamma promoters, respectively; however, GATA-3 also intrinsically suppresses T-bet and vice versa. Silencing of GATA-3/T-bet, which is influenced by factors such as cytokines, is associated with irreversible Th polarization. For the first few divisions (perhaps reflecting the situation in lymph nodes), naive Th cells retain pluripotency; after further cell divisions (perhaps under the influence of an inflammatory cytokine milieu) they may become polarized appropriately to respond to the specific environment.
Grogan
Jane L
JL
Howard Hughes Medical Institute, University of California San Francisco, 521 Parnassus Avenue, C-443, San Francisco, CA 94143-0654, USA. jgrogan@itsa.ucsf.edu
Locksley
Richard M
RM
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology; D050990:GATA3 Transcription Factor; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics; D050800:STAT6 Transcription Factor; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D007371:Interferon-gamma