Abstract
The cytokine IL-7 and its receptor, IL-7R, are critical for T cell and, in the mouse, B cell development, as well as differentiation and survival of naive T cells, and generation and maintenance of memory T cells. They are also required for innate lymphoid cell (ILC) development and maintenance, and consequently for generation of lymphoid structures and barrier defense. Here we discuss the central role of IL-7 and IL-7R in the lymphoid system and highlight the impact of their deregulation, placing a particular emphasis on their ‘dark side’ as promoters of cancer development. We also explore therapeutic implications and opportunities associated with either positive or negative modulation of the IL-7–IL-7R signaling axis.
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Acknowledgements
We thank M. Morre (Revimmune), R. Hotchkiss (Washington University), M. Cheever (University of Washington), R. Gress (NCI), I. Sereti (NIAID), N. Poirier (OSE Immunotherapeutics), C. Foley and A. Veradhachary (Fannin LLC) and E. Schafer (Baylor University) for sharing information on clinical trials, and M. Fernandes for help with draft figure preparation. J.T.B. is funded by the consolidator grant ERC CoG-648455 from the European Research Council, under the European Union’s Horizon 2020 research and innovation programme, and the FAPESP/20015/2014 and PTDC/MEC-HEM/31588/2017 grants from Fundação para a Ciência e a Tecnologia, Portugal; S.K.D. is funded by the intramural program of the US National Cancer Institute, National Institutes of Health, and the Children’s Cancer Foundation; B.S. is funded by the MRC (United Kingdom) under U117573801 and MR/P011225/1.
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J.T.B., S.K.D. and B.S. wrote the manuscript and approved its final version.
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S.K.D. is a co-inventor on the patent application “IL-7R-alpha specific antibodies for treating acute lymphoblastic leukemia” filed by the NIH (DHHS). US Patent Application No. 62/238,612.
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Barata, J.T., Durum, S.K. & Seddon, B. Flip the coin: IL-7 and IL-7R in health and disease. Nat Immunol 20, 1584–1593 (2019). https://doi.org/10.1038/s41590-019-0479-x
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DOI: https://doi.org/10.1038/s41590-019-0479-x
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