ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Differential requirement of RasGRP1 for γδ T cell development and activation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- RasGRP1 signaling is required for Vγ2+ thymocyte c-Maf expression and γδT17 lineage programming.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- γδ T Cells and Inborn Errors of Immunity.European journal of immunology · 2025Review
- Molecular insights into T cell development, activation and signal transduction (Review).Biomedical reports · 2025Review
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Thymic Epithelial Cell-Derived IL-15 and IL-15 Receptor α Chain Foster Local Environment for Type 1 Innate Like T Cell Development.Frontiers in immunology · 2021Article
- Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice.European journal of immunology · 2020Article
- Efficient CD4Cre-Mediated Conditional KRas Expression in Alveolar Macrophages and Alveolar Epithelial Cells Causes Fatal Hyperproliferative Pneumonitis.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- T cell receptor signaling for γδT cell development.Inflammation and regeneration · 2019Review
- Novel Mutations in RASGRP1 are Associated with Immunodeficiency, Immune Dysregulation, and EBV-Induced Lymphoma.Journal of clinical immunology · 2018Article
- γδTCR recruits the Syk/PI3K axis to drive proinflammatory differentiation program.The Journal of clinical investigation · 2018Article
- RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics.Nature immunology · 2016Article
- mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Development of interleukin-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus.Oncotarget · 2016Article
- Diacylglycerol Kinases in T Cell Tolerance and Effector Function.Frontiers in cell and developmental biology · 2016Review
- Targeted deletion of RasGRP1 impairs skin tumorigenesis.Carcinogenesis · 2014Article
- Diacylglycerol metabolism attenuates T-cell receptor signaling and alters thymocyte differentiation.Cell death & disease · 2013Article
- Increased cholesterol content in gammadelta (γδ) T lymphocytes differentially regulates their activation.PloS one · 2013Article
- RasGRP1, but not RasGRP3, is required for efficient thymic β-selection and ERK activation downstream of CXCR4.PloS one · 2013Article
- Regulation of Lipid Signaling by Diacylglycerol Kinases during T Cell Development and Function.Frontiers in immunology · 2013Article
- T cell Receptor Signal Transduction in T lymphocytes.Journal of clinical & cellular immunology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
γδ T (γδT) cells belong to a distinct T cell lineage that performs immune functions different from αβ T (αβT) cells. Previous studies established that Erk1/2 MAPKs are critical for positive selection of αβT cells. Additional evidence suggests that increased Erk1/2 activity promotes γδT cell generation. RasGRP1, a guanine nucleotide-releasing factor for Ras, plays an important role in positive selection of αβT cells by activating the Ras-Erk1/2 pathway. In this article, we demonstrate that RasGRP1 is critical for TCR-induced Erk1/2 activation in γδT cells, but it exerts different roles for γδT cell generation and activation. Deficiency of RasGRP1 does not obviously affect γδT cell numbers in the thymus, but it leads to increased γδT cells, particularly CD4(-)CD8(+) γδT cells, in the peripheral lymphoid organs. The virtually unhindered γδT cell development in the RasGRP1(-/-) thymus proved to be cell intrinsic, whereas the increase in CD8(+) γδT cells is caused by non-cell-intrinsic mechanisms. Our data provide genetic evidence that decreased Erk1/2 activation in the absence of RasGRP1 is compatible with γδT cell generation. Although RasGRP1 is dispensable for γδT cell generation, RasGRP1-deficient γδT cells are defective in proliferation following TCR stimulation. Additionally, RasGRP1-deficient γδT cells are impaired to produce IL-17 but not IFNγ. Together, these observations revealed that RasGRP1 plays differential roles for γδ and αβ T cell development but is critical for γδT cell proliferation and production of IL-17.
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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.