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Role of the IL-7 Receptor in γδ T-Cell Development from Hematopoietic Stem Cells

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Hematopoietic Stem Cell Biology

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Interleukin 7 (IL-7) is an essential cytokine for early lymphocyte development. The IL-7 receptor (IL-7R) transmits at least two signals in lymphocyte progenitors. One is for survival and proliferation of early and mature lymphocytes. The other is to promote V(D)J recombination of the immunoglobulin heavy (IgH) and T-cell receptor γ (TCRγ) loci. γδ T cells with a specific variable (V) γ-chain appear in successive waves in the thymus, which is controlled at the levels of hematopoietic stem cells and V(D)J recombination. The IL-7R and signal transducer and activator of transcription 5 (STAT5) control the accessibility of the TCRγ locus by interacting with STAT consensus motifs in the Jγ germline promoters and the Eγ and HsA elements. STAT5 binding to the Jγ germline promoters induces germline transcription, histone acetylation, and chromatin remodeling that make the chromatin accessible for DNA recombinase. In addition, STAT5 is recruited to the consensus motifs in the Eγ elements by cytokine stimulation and augments Eγ activity in collaboration with Runx and c-Myb. Furthermore, STAT5 directly binds to and controls the HsA element, but STAT5 indirectly activates the Vγ5 promoter. STAT5 and the TCRγ locus is an excellent model system to understand the control mechanisms of V(D)J recombination in lymphocyte antigen receptor genes.

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Acknowledgments

We thank H. Miyachi and S. Kitano for study mice, S. Hayashi, M. Kishida, and S. Kamioka for technical assistance, and members of the Ikuta lab for helpful discussions. Published and unpublished works from this laboratory were supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by grants provided by Takeda Science Foundation, Naito Foundation, Sapporo Bioscience Foundation, Astellas Foundation for Research on Metabolic Disorders, Sumitomo Foundation, Ichiro Kanehara Foundation, Uehara Memorial Foundation, Novartis Foundation (Japan) for the Promotion of Science, Shimadzu Science Foundation, TERUMO Life Science Foundation, Mitsubishi Pharma Research Foundation, and Inoue Foundation for Science. S. Tani-ichi was supported by the 21st Century COE Program of the Ministry of Education, Culture, Sports, Science and Technology to the Graduate School of Bio Studies and the Institute for Virus Research, Kyoto University.

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  1. Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan

    Koichi Ikuta & Shizue Tani-ichi

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Correspondence to Koichi Ikuta .

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  1. Duke University Medical Center, Research Drive, Durham, 27710, North Carolina, USA

    Motonari Kondo

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Ikuta, K., Tani-ichi, S. (2010). Role of the IL-7 Receptor in γδ T-Cell Development from Hematopoietic Stem Cells. In: Kondo, M. (eds) Hematopoietic Stem Cell Biology. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-60327-347-3_6

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