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Review
. 2010 Mar-Apr;88(3):244-9.
doi: 10.1038/icb.2009.114. Epub 2010 Jan 12.

Transcriptional regulation of Th2 cell differentiation

Affiliations
Review

Transcriptional regulation of Th2 cell differentiation

Jinfang Zhu. Immunol Cell Biol. 2010 Mar-Apr.

Abstract

CD4 T helper 2 (Th2) cells have critical functions in immune responses against extracellular parasites and are involved in asthma and other allergic diseases. The differentiation of naïve CD4 T cells into Th2 cells is initiated from T-cell receptor and cytokine-mediated signaling followed by upregulation of GATA3 and activation of signal transducer and activator of transcription 5 (STAT5), two indispensable events for this differentiation process. In this review, regulation of GATA3 expression and STAT5 activation and functions of these two transcription factors in inducing the expression of Th2 cytokines, cytokine receptors as well as epigenetic modification at Th2 cytokine locus are summarized. Furthermore, I present positive and negative regulatory networks important for Th2 cell commitment, selective growth of committed Th2 cells and suppression of alternative lineage fates. Finally, the difference between in vitro and in vivo Th2 differentiation is discussed.

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Figures

Figure 1
Figure 1
Positive feedback loops for Th2 cell differentiation regulated by GATA3 and STAT5. Both IL-4 and weakly stimulated TCR-mediated signaling induce the expression of Th2 master regulator GATA3. In addition, Notch and/or other signaling pathways may regulate GATA3 expression. TCR activation also results in IL-2 production and IL-2Rα upregulation. IL-2 activates STAT5 but its function may be substituted or compensated in vivo by IL-7 and TSLP, the other two STAT5 activators. GATA3 collaborates with activated STAT5 to induce IL-4 production. C-Maf, possibly regulated by GATA3, further enhances the expression of IL-4. In addition, GATA3 and STAT5 regulate the expression of both IL-2R and IL-4R. Elevated IL-4 and IL-2 production together with upregulation of IL-2R and IL-4R provide powerful positive feedback loops for promoting Th2 polarization as well as selective growth of committed Th2 cells.

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References

    1. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–2357. - PubMed
    1. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. - PubMed
    1. Paul WE, Seder RA. Lymphocyte responses and cytokines. Cell. 1994;76:241–251. - PubMed
    1. Zhu J, Paul WE. CD4 T cells: fates, functions, and faults. Blood. 2008;112:1557–1569. - PMC - PubMed
    1. Kopf M, Le Gros G, Bachmann M, Lamers MC, Bluethmann H, Kohler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993;362:245–248. - PubMed

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