IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORγt:: Impact on thymocyte development

Yu Q., ERMAN M. B., Park J., Feigenbaum L., Singer A.

JOURNAL OF EXPERIMENTAL MEDICINE, vol.200, no.6, pp.797-803, 2004 (SCI-Expanded, Scopus) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 200 Issue: 6
  • Publication Date: 2004
  • Doi Number: 10.1084/jem.20032183
  • Journal Name: JOURNAL OF EXPERIMENTAL MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.797-803
  • Acibadem Mehmet Ali Aydinlar University Affiliated: No

Abstract

Intrathymic T cell development depends on signals transduced by both T cell receptor and cytokine receptors. Early CD4(-)CD8(-) (double negative) thymocytes require interleukin (IL)-7 receptor (IL-7R) signals for survival and proliferation, but IL-7R signals are normally extinguished by the immature single positive (ISP) stage of thymocyte development. We now demonstrate that IL-7R signals inhibit expression of transcription factors TCF-1, LEF-1, and ROR-gammat that are required for the ISP to double positive (DP) transition in the thymus. In addition, we demonstrate that IL-7R signals also inhibit TCF-1 and LEF-1 expression in mature peripheral T cells. Thus, the present work has identified several important downstream target genes of IL-7R signaling in T cells and thymocytes that provide a molecular mechanism for the inhibitory influence of IL-7R signaling on DP thymocyte development. We conclude that IL-7R signals down-regulate transcription factors required for the ISP to DP transition and so must be terminated by the ISP stage of thymocyte development.