Abstract
T cells originate from early T lineage precursors that have entered the thymus and differentiate through well-defined steps. Mice deficient for the BTB/POZ domain of zinc finger protein-1 (Miz-1) almost entirely lack early T lineage precursors and have a CD4(-)CD8(-) to CD4(+)CD8(+) block causing a strong reduction in thymic cellularity. Miz-1(ΔPOZ) pro-T cells cannot differentiate in vitro and are unable to relay signals from the interleukin-7R (IL-7R). Both STAT5 phosphorylation and Bcl-2 up-regulation are perturbed. The high expression levels of SOCS1 found in Miz-1(ΔPOZ) cells probably cause these alterations. Moreover, Miz-1 can bind to the SOCS1 promoter, suggesting that Miz-1 deficiency causes a deregulation of SOCS1. Transgenic overexpression of Bcl-2 or inhibition of SOCS1 restored pro-T cell numbers and their ability to differentiate, supporting the hypothesis that Miz-1 is required for the regulation of the IL-7/IL-7R/STAT5/Bcl-2 signaling pathway by monitoring the expression levels of SOCS1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / genetics*
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Cell Differentiation / immunology
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Cell Lineage / genetics*
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Cell Lineage / immunology
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Cell Survival / genetics
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Cell Survival / immunology
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Cells, Cultured
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Gene Expression Regulation
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Kruppel-Like Transcription Factors / chemistry
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / physiology*
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Lymphoid Progenitor Cells / immunology
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Lymphoid Progenitor Cells / metabolism
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Lymphoid Progenitor Cells / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Protein Structure, Tertiary
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Receptors, Interleukin-7 / physiology*
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins / genetics
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Suppressor of Cytokine Signaling Proteins / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / physiology
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / physiology
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Zinc Fingers / genetics
Substances
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Kruppel-Like Transcription Factors
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Receptors, Interleukin-7
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Socs1 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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Transcription Factors
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ZBTB17 protein, human