ArticleProceedings of the National Academy of Sciences of the United States of America2012
TCR signaling via Tec kinase ITK and interferon regulatory factor 4 (IRF4) regulates CD8+ T-cell differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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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
67 citing papers in PubMed, 102 citations in OpenAlex.
- Virtual memory CD8⁺ T cells in aging: heterogeneity, bystander protection, inflammatory potential, and inhibitory regulation.Immunity & ageing : I & A · 2026Review
- Targeting interleukin-2-inducible T cell kinase ameliorates immune-mediated aplastic anemia.Cancer immunology, immunotherapy : CII · 2025Article
- Hair regrowth in alopecia areata and re-pigmentation in vitiligo in response to treatment: Commonalities and differences.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Deciphering the deterministic role of TCR signaling in T cell fate determination.Frontiers in immunology · 2025Review
- Synthesis and characterization of soquelitinib a selective ITK inhibitor that modulates tumor immunity.npj drug discovery · 2024Article
- Perinatal thymic-derived CD8αβ-expressing γδ T cells are innate IFN-γ producers that expand in IL-7R-STAT5B-driven neoplasms.Nature immunology · 2024Article
- Article
- The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation.Science (New York, N.Y.) · 2023Article
- Regulation of effector and memory CD8 + T cell differentiation: a focus on orphan nuclear receptor NR4A family, transcription factor, and metabolism.Immunologic research · 2023Review
- A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer.Nature communications · 2023Article
- Virtual Memory CD8Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Review
- Inflammatory Cytokines That Enhance Antigen Responsiveness of Naïve CD8International journal of molecular sciences · 2022Article
- Differentiation and homeostasis of effector Treg cells are regulated by inositol polyphosphates modulating CaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Inherited immunodeficiencies associated with proximal and distal defects in T cell receptor signaling and co-signaling.Biomedical journal · 2022Review
- Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling.Science immunology · 2021Article
- Hierarchy of signaling thresholds downstream of the T cell receptor and the Tec kinase ITK.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Interferon regulatory factor 4 controls effector functions of CD8Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecularly targeted therapies for relapsed and refractory peripheral T-cell lymphomas.Seminars in hematology · 2021Article
- Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.Cell reports. Medicine · 2020Article
- The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8Proceedings of the National Academy of Sciences of the United States of America · 2020Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
CD8(+) T-cell development in the thymus generates a predominant population of conventional naive cells, along with minor populations of "innate" T cells that resemble memory cells. Recent studies analyzing a variety of KO or knock-in mice have indicated that impairments in the T-cell receptor (TCR) signaling pathway produce increased numbers of innate CD8(+) T cells, characterized by their high expression of CD44, CD122, CXCR3, and the transcription factor, Eomesodermin (Eomes). One component of this altered development is a non-CD8(+) T cell-intrinsic role for IL-4. To determine whether reduced TCR signaling within the CD8(+) T cells might also contribute to this pathway, we investigated the role of the transcription factor, IFN regulatory factor 4 (IRF4). IRF4 is up-regulated following TCR stimulation in WT T cells; further, this up-regulation is impaired in T cells treated with a small-molecule inhibitor of the Tec family tyrosine kinase, IL-2 inducible T-cell kinase (ITK). In contrast to WT cells, activation of IRF4-deficient CD8(+) T cells leads to rapid and robust expression of Eomes, which is further enhanced by IL-4 stimulation. In addition, inhibition of ITK together with IL-4 increases Eomeso up-regulation. These data indicate that ITK signaling promotes IRF4 up-regulation following CD8(+) T-cell activation and that this signaling pathway normally suppresses Eomes expression, thereby regulating the differentiation pathway of CD8(+) T cells.
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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.