IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORgammat: impact on thymocyte development.
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 RORgammat 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.
Yu
Qing
Q
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm. 4B36, Bethesda, MD 20892, USA.
Erman
Batu
B
Park
Jung-Hyun
JH
Feigenbaum
Lionel
L
Singer
Alfred
A
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D051538:Hepatocyte Nuclear Factor 1-alpha; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D051746:ZAP-70 Protein-Tyrosine Kinase
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020395:Receptors, Interleukin-7; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse