A Chimeric IL-7Rα/IL-2Rβ Receptor Promotes the Differentiation of T Cell Progenitors into B Cells and Type 2 Innate Lymphoid Cells

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  • Akihiro Shimba
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,
  • Shizue Tani-ichi
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,
  • Guangwei Cui
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,
  • Satoru Munakata
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,
  • Kyoko Masuda
    Laboratory of Immunology, Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,
  • Satsuki Kitano
    Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,
  • Shinya Abe
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,
  • Hitoshi Miyachi
    Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,
  • Hiroshi Kawamoto
    Laboratory of Immunology, Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,
  • Koichi Ikuta
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,

Bibliographic Information

Published
2024-08-14
Resource Type
journal article
Rights Information
  • https://academic.oup.com/pages/standard-publication-reuse-rights
DOI
  • 10.4049/jimmunol.2300483
Publisher
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title> <jats:p>IL-7 and IL-2 are evolutionarily related cytokines that play critical roles in the development and expansion of immune cells. Although both IL-7R and IL-2R activate similar signaling molecules, whether their signals have specific or overlapping functions during lymphocyte differentiation remains unclear. To address this question, we generated IL-7R α-chain (IL-7Rα)/IL-2R β-chain (IL-24β) (72R) knock-in mice expressing a chimeric receptor consisting of the extracellular domain of IL-7Rα and the intracellular domain of IL-2Rβ under the control of the endogenous IL-7Rα promoter. Notably, this 72R receptor induced higher levels of STAT5 and Akt phosphorylation in T cells. In the periphery of 72R mice, the number of T cells, B cells, and type 2 innate lymphoid cells (ILC2s) was increased, whereas early T cell progenitors and double-negative 2 thymocytes were reduced in the thymus. In addition, cell proliferation and Notch signaling were impaired in the early thymocytes of 72R mice, leading to their differentiation into thymic B cells. Interestingly, ILC2s were increased in the thymus of 72R mice. Early T cell progenitors from 72R mice, but not from wild-type mice, differentiated into NK cells and ILC2-like cells when cocultured with a thymic stromal cell line. Thus, this study indicates that the chimeric 72R receptor transduces more robust signals than the authentic IL-7Rα, thereby inducing the alternative differentiation of T cell progenitors into other cell lineages. This suggests that cytokine receptors may provide instructive signals for cell fate decisions.</jats:p>

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