ArticleJournal of immunology (Baltimore, Md. : 1950)2015
A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed, 39 citations in OpenAlex.
- Targeted inhibition of ITK activity with anti-CD3 antibody-modified calcium silicate nanoparticles loaded with novel 7H-Pyrrolo[2,3-d]pyrimidine derivatives for treating aplastic anemia.Journal of nanobiotechnology · 2026Article
- Voclosporin shows protective effect and intestinal barrier enforcement in experimental colitis.Frontiers in medicine · 2026Article
- Regulation of TCR-induced Transcriptional Kinetics by Interleukin 2-inducible T Cell Kinase (ITK) in CD8bioRxiv : the preprint server for biology · 2025Article
- Advancements in research on the cardiovascular toxicity caused by TEC family kinases inhibitors.Frontiers in pharmacology · 2025Review
- Combinatorial inhibition of Tec kinases BTK and ITK is beneficial in ameliorating murine sclerodermatous chronic graft versus host disease.Bone marrow transplantation · 2023Article
- T-helper cells flexibility: the possibility of reprogramming T cells fate.Frontiers in immunology · 2023Review
- Article
- Tackling Inflammatory Bowel Diseases: Targeting Proinflammatory Cytokines and Lymphocyte Homing.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Regulation of the Tec family of non-receptor tyrosine kinases in cardiovascular disease.Cell death discovery · 2022Review
- Targeting ITK signaling for T cell-mediated diseases.iScience · 2021Review
- The Tyrosine Kinase Tec Regulates Effector Th17 Differentiation, Pathogenicity, and Plasticity in T-Cell-Driven Intestinal Inflammation.Frontiers in immunology · 2021Article
- Role of the IL-2 inducible tyrosine kinase ITK and its inhibitors in disease pathogenesis.Journal of molecular medicine (Berlin, Germany) · 2020Review
- CD8ImmunoHorizons · 2020Article
- ITK inhibition promotes long-term survival of cardiac allografts by regulating T cell PLCγ phosphorylation.American journal of translational research · 2020Article
- The Tec kinase ITK is essential for ILC2 survival and epithelial integrity in the intestine.Nature communications · 2019Article
- Differential T-cell receptor signals for T helper cell programming.Immunology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
In T cells, the Tec kinases IL-2-inducible T cell kinase (ITK) and resting lymphocyte kinase (RLK) are activated by TCR stimulation and are required for optimal downstream signaling. Studies of CD4(+) T cells from Itk(-/-) and Itk(-/-)Rlk(-/-) mice have indicated differential roles of ITK and RLK in Th1, Th2, and Th17 differentiation and cytokine production. However, these findings are confounded by the complex T cell developmental defects in these mice. In this study, we examine the consequences of ITK and RLK inhibition using a highly selective and potent small molecule covalent inhibitor PRN694. In vitro Th polarization experiments indicate that PRN694 is a potent inhibitor of Th1 and Th17 differentiation and cytokine production. Using a T cell adoptive transfer model of colitis, we find that in vivo administration of PRN694 markedly reduces disease progression, T cell infiltration into the intestinal lamina propria, and IFN-γ production by colitogenic CD4(+) T cells. Consistent with these findings, Th1 and Th17 cells differentiated in the presence of PRN694 show reduced P-selectin binding and impaired migration to CXCL11 and CCL20, respectively. Taken together, these data indicate that ITK plus RLK inhibition may have therapeutic potential in Th1-mediated inflammatory diseases.
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What Socratic holds
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 Socratic graph.