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GATA-3 transcriptional memory in T helper lymphocytes a mathematical model of steady-state and temporal behaviour

Date: 
Monday 24th September 2001 - 16:10 to 17:10
Venue: 
INI Seminar Room 1
Session Title: 
Vertical Integration in Biology: From Molecules to Organisms
Abstract: 
T helper (Th) lymphocytes are central regulators of adaptive immune responses. Upon initial contact with antigen presenting cells, they differentiate into Th1 or Th2 cells. Th1 cells express activators of cellular immune responses such as IFN gamma, while Th2 cells stimulate humoral immune responses through the production of IL-4. The Th1/Th2 differentiation is determined by costimulatory cytokine signals acting on specific transcription factors. Recently, the transcription factor GATA-3 has been shown to induce the Th2 program of cytokine expression and to exhibit autoactivation of its expression. By means of a mathematical model of GATA-3 expression it is demonstrated how this autoregulatory loop can lead to an bistable switch between low and upregulated levels of GATA-3. On the basis of this mechanism, the establishment of a transcriptional memory for IL-4 expression through transient activation of the JAK/STAT6 pathway is analysed and compared with experimental results.
University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons