ArticleJournal of immunology (Baltimore, Md. : 1950)2014
IL-2-inducible T cell kinase tunes T regulatory cell development and is required for suppressive function.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 46 citations in OpenAlex.
- The phospholipid kinase PIKFYVE is essential for Th17 differentiation.The Journal of experimental medicine · 2025Article
- The kinase ITK controls a CaScience signaling · 2024Article
- TCF-1 negatively regulates the suppressive ability of canonical and noncanonical Tregs.Journal of leukocyte biology · 2023Article
- Inhibition of ITK Signaling Causes Amelioration in Sepsis-Associated Neuroinflammation and Depression-like State in Mice.International journal of molecular sciences · 2023Article
- Article
- ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation.Communications biology · 2022Article
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
- Interleukin-2-inducible T-cell kinase (Itk) signaling regulates potent noncanonical regulatory T cells.Clinical and translational medicine · 2021Article
- Review
- TCR/ITK Signaling in Type 1 Regulatory T cells.Advances in experimental medicine and biology · 2021Article
- Role of the IL-2 inducible tyrosine kinase ITK and its inhibitors in disease pathogenesis.Journal of molecular medicine (Berlin, Germany) · 2020Review
- TCR Signal Strength and Antigen Affinity Regulate CD8Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Ibrutinib resistance in a patient with transformed diffuse large B-cell lymphoma from primary pulmonary mucosa-associated lymphoid tissue lymphoma.Cancer biology & therapy · 2020Article
- Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development.The Journal of pathology · 2020Article
- Tuning T helper cell differentiation by ITK.Biochemical Society transactions · 2020Review
- ITK inhibition promotes long-term survival of cardiac allografts by regulating T cell PLCγ phosphorylation.American journal of translational research · 2020Article
- Non-receptor tyrosine kinase signaling in autoimmunity and therapeutic implications.Pharmacology & therapeutics · 2019Review
- Genetic Deficiency and Biochemical Inhibition of ITK Affect Human Th17, Treg, and Innate Lymphoid Cells.Journal of clinical immunology · 2019Article
- Thymic regulatory T cells arise via two distinct developmental programs.Nature immunology · 2019Article
- Interleukin-2-Inducible T-Cell Kinase Deficiency Impairs Early Pulmonary Protection AgainstFrontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
IL-2-inducible T cell kinase (ITK) is a key signaling mediator downstream of TCR, mediating T cell positive selection, as well as innate T cell and CD4(+) Th2/Th17 differentiation. In this article, we show that ITK also negatively tunes IL-2-induced expansion of conventional Foxp3-expressing regulatory T cells (Tregs). In vivo, Treg abundance is inversely correlated with ITK expression, and inducible Treg development is inversely dependent on ITK kinase activity. While Treg development normally requires both hematopoietic and thymic MHC class 2 (MHC2) expression, the absence of ITK allows Treg development with MHC2 expression in either compartment, with preference for selection by thymic MHC2, suggesting a gatekeeper role for ITK in ensuring that only Tregs selected by both thymic and hematopoietic MHC2 survive selection. Although ITK suppresses Treg development and is not required for maintenance of neuropilin-1-positive natural Tregs in the periphery, it is indispensable for Treg functional suppression of naive CD4(+) T cell-induced colitis in Rag(-/-) recipients. ITK thus regulates the development and function of Tregs.
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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.