Limits...
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.

Show MeSH
Effect of cotransduction of GATA3 and Runx1 on Th2 cell differentiation. (A) Naive CD4+ T cells were isolated from the spleens of wild-type and GATA3-transgenic mice, TCR-stimulated, infected by retroviruses carrying pMX or pMX-Runx1, and cultured in the presence of IL-2. The GFP+ population was sorted and reactivated via TCR. The cytokines secreted into the culture supernatant were measured by ELISA. The values obtained for the pMX-Runx1–infected cells are presented as percent inhibition of secretion, taking the values observed for the pMX-infected cells to be 100%. (B) Naive CD4+ T cells were isolated from the spleens of IL-4R (−/−) mice, TCR-stimulated, coinfected by pMX-GFP and pMX-rat CD2 retroviruses as indicated, and cultured in the presence of IL-2. The rat CD2+ population was sorted, TCR-stimulated, and processed for flow cytometrical analysis of intracellular IL-4. Data are representative of two independent experiments.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196077&req=5

fig6: Effect of cotransduction of GATA3 and Runx1 on Th2 cell differentiation. (A) Naive CD4+ T cells were isolated from the spleens of wild-type and GATA3-transgenic mice, TCR-stimulated, infected by retroviruses carrying pMX or pMX-Runx1, and cultured in the presence of IL-2. The GFP+ population was sorted and reactivated via TCR. The cytokines secreted into the culture supernatant were measured by ELISA. The values obtained for the pMX-Runx1–infected cells are presented as percent inhibition of secretion, taking the values observed for the pMX-infected cells to be 100%. (B) Naive CD4+ T cells were isolated from the spleens of IL-4R (−/−) mice, TCR-stimulated, coinfected by pMX-GFP and pMX-rat CD2 retroviruses as indicated, and cultured in the presence of IL-2. The rat CD2+ population was sorted, TCR-stimulated, and processed for flow cytometrical analysis of intracellular IL-4. Data are representative of two independent experiments.

Mentions: We next examined whether GATA3 transduction could recover Th2 cytokine production in the pMX-Runx1–infected cells, using GATA3-transgenic mice. CD4+ T cells were prepared from wild-type and transgenic mice, stimulated by anti-CD3/anti-CD28 antibodies, and infected by pMX or pMX-Runx1 retroviruses. The GFP+ cells were sorted and restimulated via TCR, and the amounts of secreted cytokines were assayed. In Fig. 6 A, the values obtained for the pMX-Runx1-infected cells are presented as percent inhibition of secretion, taking the values obtained for the pMX-infected cells to be 100%. The percent inhibition of IL-4 and IL-5 secretion in the GATA3-transgenic cells was roughly two thirds and one half of that in the wild-type cells, respectively. GATA3 did not cause a significant difference in the IFN-γ production of the wild-type and transgenic 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)

Effect of cotransduction of GATA3 and Runx1 on Th2 cell differentiation. (A) Naive CD4+ T cells were isolated from the spleens of wild-type and GATA3-transgenic mice, TCR-stimulated, infected by retroviruses carrying pMX or pMX-Runx1, and cultured in the presence of IL-2. The GFP+ population was sorted and reactivated via TCR. The cytokines secreted into the culture supernatant were measured by ELISA. The values obtained for the pMX-Runx1–infected cells are presented as percent inhibition of secretion, taking the values observed for the pMX-infected cells to be 100%. (B) Naive CD4+ T cells were isolated from the spleens of IL-4R (−/−) mice, TCR-stimulated, coinfected by pMX-GFP and pMX-rat CD2 retroviruses as indicated, and cultured in the presence of IL-2. The rat CD2+ population was sorted, TCR-stimulated, and processed for flow cytometrical analysis of intracellular IL-4. Data are representative of two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196077&req=5

fig6: Effect of cotransduction of GATA3 and Runx1 on Th2 cell differentiation. (A) Naive CD4+ T cells were isolated from the spleens of wild-type and GATA3-transgenic mice, TCR-stimulated, infected by retroviruses carrying pMX or pMX-Runx1, and cultured in the presence of IL-2. The GFP+ population was sorted and reactivated via TCR. The cytokines secreted into the culture supernatant were measured by ELISA. The values obtained for the pMX-Runx1–infected cells are presented as percent inhibition of secretion, taking the values observed for the pMX-infected cells to be 100%. (B) Naive CD4+ T cells were isolated from the spleens of IL-4R (−/−) mice, TCR-stimulated, coinfected by pMX-GFP and pMX-rat CD2 retroviruses as indicated, and cultured in the presence of IL-2. The rat CD2+ population was sorted, TCR-stimulated, and processed for flow cytometrical analysis of intracellular IL-4. Data are representative of two independent experiments.
Mentions: We next examined whether GATA3 transduction could recover Th2 cytokine production in the pMX-Runx1–infected cells, using GATA3-transgenic mice. CD4+ T cells were prepared from wild-type and transgenic mice, stimulated by anti-CD3/anti-CD28 antibodies, and infected by pMX or pMX-Runx1 retroviruses. The GFP+ cells were sorted and restimulated via TCR, and the amounts of secreted cytokines were assayed. In Fig. 6 A, the values obtained for the pMX-Runx1-infected cells are presented as percent inhibition of secretion, taking the values obtained for the pMX-infected cells to be 100%. The percent inhibition of IL-4 and IL-5 secretion in the GATA3-transgenic cells was roughly two thirds and one half of that in the wild-type cells, respectively. GATA3 did not cause a significant difference in the IFN-γ production of the wild-type and transgenic 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