Transcription Factors and Helper T Cell Lineage Determination

Science's STKE  25 Jan 2005:
Vol. 2005, Issue 268, pp. tw41
DOI: 10.1126/stke.2682005tw41

In helper T (Th) cells, cell fate is primarily determined by the transcription factors GATA-3, which directs Th2-type cells, and T-bet, which regulates Th1 lineage choice. Hwang et al. found that during the early stages of a T helper precursor's decision to become a Th1 cell, T-bet has an unusual means of repressing the Th2-promoting effects of GATA-3. After T cell stimulation and under the right polarizing conditions for Th1 cells, T-bet becomes phosphorylated by the tyrosine kinase, ITK, which allows it to bind GATA-3 . This process prevents it from interacting with its Th2 cytokine target genes. This study reveals a further means by which transcription factors may directly cross-regulate one another in specifying cell lineage fate.

E. S. Hwang, S. J. Szabo, P. L. Schwartzberg, L. H. Glimcher, T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307, 430-433 (2005). [Abstract] [Full Text]