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The Runx1 transcription factor inhibits the differentiation of naive CD4+ T cells into the Th2 lineage by repressing GATA3 expression.

Komine O, Hayashi K, Natsume W, Watanabe T, Seki Y, Seki N, Yagi R, Sukzuki W, Tamauchi H, Hozumi K, Habu S, Kubo M, Satake M - J. Exp. Med. (2003)

Bottom Line: In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression.Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased.We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: Research Institute for Biological Sciences, Tokyo University of Science, Noda, Japan.

ABSTRACT
Differentiation of naive CD4+ T cells into helper T (Th) cells is controlled by a combination of several transcriptional factors. In this study, we examined the functional role of the Runx1 transcription factor in Th cell differentiation. Naive T cells from transgenic mice expressing a dominant interfering form of Runx1 exhibited enhanced interleukin 4 production and efficient Th2 differentiation. In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression. Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased. We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation.

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Expression of endogenous Runx1 and GATA3 proteins in CD4+ T cells. (A) Naive CD4+ T cells were isolated from the spleens of mice and cultured under the Th1- or Th2-condition for 7 d. Protein extracts were processed for immunoblot analysis, using anti-Runx1 antibody. Protein extracted from the pMX-Runx1-infected or pMX-infected, TCR-stimulated CD4+ T cells was also probed with the same antibody. (B) Protein was extracted at indicated hour after culturing in the Th2- or Th1-condition. (C) Naive CD4+ T cells were treated or not by anti-CD3/anti-CD28 antibodies for 24 h. Extracts containing 1, 3, and 5 μg protein, respectively, were processed for EMSA. Data are representative of two independent experiments.
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fig7: Expression of endogenous Runx1 and GATA3 proteins in CD4+ T cells. (A) Naive CD4+ T cells were isolated from the spleens of mice and cultured under the Th1- or Th2-condition for 7 d. Protein extracts were processed for immunoblot analysis, using anti-Runx1 antibody. Protein extracted from the pMX-Runx1-infected or pMX-infected, TCR-stimulated CD4+ T cells was also probed with the same antibody. (B) Protein was extracted at indicated hour after culturing in the Th2- or Th1-condition. (C) Naive CD4+ T cells were treated or not by anti-CD3/anti-CD28 antibodies for 24 h. Extracts containing 1, 3, and 5 μg protein, respectively, were processed for EMSA. Data are representative of two independent experiments.

Mentions: Runx1, when overexpressed, can negatively regulate GATA3 expression. To explore a relationship between Runx1 and GATA3 under a physiological condition, we first examined the expression pattern of endogenous proteins in naive CD4+, Th2, and Th1 cells by immunoblot analysis (Fig. 7 A). The Runx1 protein was evident as a 56-kD band in naive CD4+ cells, but not in fully differentiated Th1 cells for 7 d. In Th2 cells, a subtle amount of Runx1 protein might be present. Therefore, Runx1 appears to play its role, if any, in naive but not in differentiated Th1 nor Th2 cells.


The Runx1 transcription factor inhibits the differentiation of naive CD4+ T cells into the Th2 lineage by repressing GATA3 expression.

Komine O, Hayashi K, Natsume W, Watanabe T, Seki Y, Seki N, Yagi R, Sukzuki W, Tamauchi H, Hozumi K, Habu S, Kubo M, Satake M - J. Exp. Med. (2003)

Expression of endogenous Runx1 and GATA3 proteins in CD4+ T cells. (A) Naive CD4+ T cells were isolated from the spleens of mice and cultured under the Th1- or Th2-condition for 7 d. Protein extracts were processed for immunoblot analysis, using anti-Runx1 antibody. Protein extracted from the pMX-Runx1-infected or pMX-infected, TCR-stimulated CD4+ T cells was also probed with the same antibody. (B) Protein was extracted at indicated hour after culturing in the Th2- or Th1-condition. (C) Naive CD4+ T cells were treated or not by anti-CD3/anti-CD28 antibodies for 24 h. Extracts containing 1, 3, and 5 μg protein, respectively, were processed for EMSA. Data are representative of two independent experiments.
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Related In: Results  -  Collection

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fig7: Expression of endogenous Runx1 and GATA3 proteins in CD4+ T cells. (A) Naive CD4+ T cells were isolated from the spleens of mice and cultured under the Th1- or Th2-condition for 7 d. Protein extracts were processed for immunoblot analysis, using anti-Runx1 antibody. Protein extracted from the pMX-Runx1-infected or pMX-infected, TCR-stimulated CD4+ T cells was also probed with the same antibody. (B) Protein was extracted at indicated hour after culturing in the Th2- or Th1-condition. (C) Naive CD4+ T cells were treated or not by anti-CD3/anti-CD28 antibodies for 24 h. Extracts containing 1, 3, and 5 μg protein, respectively, were processed for EMSA. Data are representative of two independent experiments.
Mentions: Runx1, when overexpressed, can negatively regulate GATA3 expression. To explore a relationship between Runx1 and GATA3 under a physiological condition, we first examined the expression pattern of endogenous proteins in naive CD4+, Th2, and Th1 cells by immunoblot analysis (Fig. 7 A). The Runx1 protein was evident as a 56-kD band in naive CD4+ cells, but not in fully differentiated Th1 cells for 7 d. In Th2 cells, a subtle amount of Runx1 protein might be present. Therefore, Runx1 appears to play its role, if any, in naive but not in differentiated Th1 nor Th2 cells.

Bottom Line: In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression.Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased.We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: Research Institute for Biological Sciences, Tokyo University of Science, Noda, Japan.

ABSTRACT
Differentiation of naive CD4+ T cells into helper T (Th) cells is controlled by a combination of several transcriptional factors. In this study, we examined the functional role of the Runx1 transcription factor in Th cell differentiation. Naive T cells from transgenic mice expressing a dominant interfering form of Runx1 exhibited enhanced interleukin 4 production and efficient Th2 differentiation. In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression. Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased. We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation.

Show MeSH