Molecular aspects of T-cell differentiation.
Differentiated T helper 1 (Th1) and T helper 2 (Th2) T-cells show striking differences in their patterns of cytokine expression. This process is initiated by stimulation with antigen and the cytokines IL-12 and IL-4, respectively, and requires antigen-induced transcription factors such as NFAT and cytokine-induced transcription factors such as STAT4, induced by IL-12, and STAT6, induced by IL-4. This results in induction and maintained expression of subset-specific transcription factors including T-bet in Th1 cells and GATA3 in Th2 cells, which are involved in ensuring the commitment of T-cells to Th1 or Th2 lineages. Here we review the signalling pathways and transcription factors that mediate T-cell differentiation, and describe the epigenetic changes in chromatin structure, locus accessibility and DNA methylation that are known to accompany this process.
Rao
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Center for Blood Research, Department of Pathology, Harvard Medical School, Warren Alpert Building, 200 Longwood Avenue, Boston, MA 02115, USA.
Avni
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D001424:Bacterial Infections / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D002843:Chromatin / Q000648:ultrastructure; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D019175:DNA Methylation; D003850:Deoxyribonuclease I / Q000378:metabolism; D005246:Feedback; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D010272:Parasitic Diseases / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology*
D002843:Chromatin; D016207:Cytokines; D014157:Transcription Factors; D007371:Interferon-gamma; D003850:Deoxyribonuclease I