ArticleThe Journal of experimental medicine2006
IL-7 promotes T cell proliferation through destabilization of p27Kip1.
Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 90 citations in OpenAlex.
- Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial.JCI insight · 2018Trial
- The Interleukin-7 Receptor Signaling Pathway and Its Perturbation in Immunodeficiency, Autoimmune Disease and Lymphoid Malignancy.Biomolecules · 2026Review
- Article
- Lymphopenia and Mechanisms of T-Cell Regeneration.Cell and tissue biology · 2022Article
- Diagnosis and Treatment of a Patient With Severe Combined Immunodeficiency Due to a Novel Homozygous Mutation in the IL-7Rα Chain.Frontiers in immunology · 2022Article
- IL-7: A promising adjuvant ensuring effective T cell responses and memory in combination with cancer vaccines?Frontiers in immunology · 2022Review
- The Broad Immunomodulatory Effects of IL-7 and Its Application In Vaccines.Frontiers in immunology · 2021Review
- Interleukin (IL)-7 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- IL-7 induces sCD127 release and mCD127 downregulation in human CD8European journal of immunology · 2020Article
- Article
- Cancer Conditioned Medium Modulates Functional and Phenotypic Properties of HumanTissue engineering and regenerative medicine · 2019Article
- Inhibiting Janus Kinase 1 and BCL-2 to treat T cell acute lymphoblastic leukemia with IL7-Rα mutations.Oncotarget · 2018Article
- Spontaneous T Cell Proliferation: A Physiologic Process to Create and Maintain Homeostatic Balance and Diversity of the Immune System.Frontiers in immunology · 2018Review
- Targeting Homeostatic T Cell Proliferation to Control Beta-Cell Autoimmunity.Current diabetes reports · 2016Review
- Interleukin-7 Modulates Anti-Tumor CD8+ T Cell Responses via Its Action on Host Cells.PloS one · 2016Article
- Interferon-α inhibits CD4 T cell responses to interleukin-7 and interleukin-2 and selectively interferes with Akt signaling.Journal of leukocyte biology · 2015Article
- Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1.Autophagy · 2015Article
- Article
- Adaptive immunity to murine skin commensals.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- T-cell intrinsic and extrinsic mechanisms of p27Kip1 in the regulation of CD8 T-cell memory.Immunology and cell biology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Interleukin (IL)-7 is required for survival and homeostatic proliferation of T lymphocytes. The survival effect of IL-7 is primarily through regulation of Bcl-2 family members; however, the proliferative mechanism is unclear. It has not been determined whether the IL-7 receptor actually delivers a proliferative signal or whether, by promoting survival, proliferation results from signals other than the IL-7 receptor. We show that in an IL-7-dependent T cell line, cells protected from apoptosis nevertheless underwent cell cycle arrest after IL-7 withdrawal. This arrest was accompanied by up-regulation of the cyclin-dependent kinase inhibitor p27Kip1 through a posttranslational mechanism. Overexpression of p27Kip1 induced G1 arrest in the presence of IL-7, whereas knockdown of p27Kip1 by small interfering RNA promoted S phase entry after IL-7 withdrawal. CD4 or CD8 T cells transferred into IL-7-deficient hosts underwent G1 arrest, whereas 27Kip1-deficient T cells underwent proliferation. We observed that IL-7 withdrawal activated protein kinase C (PKC)theta and that inhibition of PKCtheta with a pharmacological inhibitor completely blocked the rise of p27Kip1 and rescued cells from G1 arrest. The conventional pathway to breakdown of p27Kip1 is mediated by S phase kinase-associated protein 2; however, our evidence suggests that PKCtheta acts via a distinct, unknown pathway inducing G1 arrest after IL-7 withdrawal from T cells. Hence, IL-7 maintains T cell proliferation through a novel pathway of p27Kip1 regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.