An Essential Role for the Transcription Factor Runx1 in T Cell Maturation

Fan Chi Hsu, Michael J. Shapiro, Barsha Dash, Chien Chang Chen, Megan M. Constans, Ji Young Chung, Sinibaldo R. Romero Arocha, Paul J. Belmonte, Meibo W. Chen, Douglas C. McWilliams, Virginia M Shapiro

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4 Scopus citations

Abstract

The transcription factor Runx1 has essential roles throughout hematopoiesis. Here, we demonstrate that Runx1 is critical for T cell maturation. Peripheral naive CD4+ T cells from CD4-cre Runx1 cKO mice are phenotypically and functionally immature as shown by decreased production of TNF-α upon TCR stimulation. The loss of peripheral CD4+ T cells in CD4-cre Runx1 cKO mice is not due to defects in homeostasis or decreased expression of IL-7Rα, as transgenic expression of IL-7Rα does not rescue the loss of CD4+ T cells. Rather, immature Runx1-deficient CD4+ T cells are eliminated in the periphery by the activation and fixation of the classical complement pathway. In the thymus, there is a severe block in all aspects of intrathymic T cell maturation, although both positive and negative selection are unaltered. Thus, loss of Runx1 leads to the earliest characterized block in post-positive selection intrathymic maturation of CD4 T cells.

Original languageEnglish (US)
Article number23533
JournalScientific Reports
Volume6
DOIs
StatePublished - Mar 29 2016

ASJC Scopus subject areas

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    Hsu, F. C., Shapiro, M. J., Dash, B., Chen, C. C., Constans, M. M., Chung, J. Y., Romero Arocha, S. R., Belmonte, P. J., Chen, M. W., McWilliams, D. C., & Shapiro, V. M. (2016). An Essential Role for the Transcription Factor Runx1 in T Cell Maturation. Scientific Reports, 6, [23533]. https://doi.org/10.1038/srep23533