Runx3 regulates integrin αE/CD103 and CD4 expression during development of CD4-/CD8+ T cells

Baerbel Grueter, Michaela Petter, Takeshi Egawa, Kirsten Laule-Kilian, Christine J. Aldrian, Andreas Wuerch, Yvonne Ludwig, Hidehiro Fukuyama, Hedda Wardemann, Ralph Waldschuetz, Tarik Möröy, Ichiro Taniuchi, Viktor Steimle, Dan R. Littman, Marc Ehlers

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Abstract

During thymic T cell development, immature CD4+CD8+ double-positive (DP) thymocytes develop either into CD4+CD8 - Th cells or CD4-CD8+ CTLs. Differentially expressed primary factors inducing the fate of these cell types are still poorly described. The transcription factor Runx3/AML-2 Runx, rust dominant factor; AML, acute myeloid leukemia is expressed specifically during the development of CD8 single-positive (SP) thymocytes, where it silences CD4 expression. Deletion of murine Runx3 results in a reduction of CD8 SP T cells and concomitant accumulation of CD4+CD8+ T cells, which cannot down-regulate CD4 expression in the thymus and periphery. In this study we have investigated the role of Runx3 during thymocyte development and CD4 silencing and have identified integrin αE/CD103 on CD8 SP T cells as a new potential target gene of Runx3. We demonstrate that Runx3 is necessary not only to repress CD4, but also to induce CD103 expression during development of CDS SP T cells. In addition, transgenic overexpression of Runx3 reduced CD4 expression during development of DP thymocytes, leading to a reduced number of CD4 SP thymocytes and an increased number of CDS SP thymocytes. This reversal is not caused by redirection of specific MHC class II-restricted cells to the CD8 lineage. Overexpression of Runx3 also up-regulated CD103 expression on a subpopulation of CD4 SP T cells with characteristics of regulatory T cells. Thus, Runx3 is a main regulator of CD4 silencing and CD103 induction and thus contributes to the phenotype of CD8 SP T cells during thymocyte development.

Original languageEnglish
Pages (from-to)1694-1705
Number of pages12
JournalJournal of Immunology
Volume175
Issue number3
StatePublished - Aug 1 2005
Externally publishedYes

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    Grueter, B., Petter, M., Egawa, T., Laule-Kilian, K., Aldrian, C. J., Wuerch, A., Ludwig, Y., Fukuyama, H., Wardemann, H., Waldschuetz, R., Möröy, T., Taniuchi, I., Steimle, V., Littman, D. R., & Ehlers, M. (2005). Runx3 regulates integrin αE/CD103 and CD4 expression during development of CD4-/CD8+ T cells. Journal of Immunology, 175(3), 1694-1705.