ArticleeLife2013
Rasgrp1 mutation increases naive T-cell CD44 expression and drives mTOR-dependent accumulation of Helios⁺ T cells and autoantibodies.
Article in eLife, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- Rasgrp1-Mediated Dampening of EGFR Signals Supports Coordinated Mammary Gland Development.Cells · 2026Article
- Cathepsin L-dependent positive selection shapes clonal composition and functional fitness of CD4Nature immunology · 2025Article
- Elucidation and application of the neuroimmune axis between depression and autoimmune diseases: A genome wide and cohort study.PloS one · 2025Article
- Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.Cell cycle (Georgetown, Tex.) · 2024Review
- Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells.Nature genetics · 2022Article
- Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients.Biomolecules · 2022Article
- Hyperactive PI3Kδ predisposes naive T cells to activation via aerobic glycolysis programs.Cellular & molecular immunology · 2021Article
- Article
- Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity.European journal of immunology · 2021Article
- Article
- Ras GEF Mouse Models for the Analysis of Ras Biology and Signaling.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Regulation of the Small GTPase Ras and Its Relevance to Human Disease.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Metabolic Choice Tunes Foxp3+ Regulatory T Cell Function.Advances in experimental medicine and biology · 2021Article
- Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions.Nature immunology · 2020Article
- CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney.Physiological reports · 2020Article
- mTOR signaling at the crossroads of environmental signals and T-cell fate decisions.Immunological reviews · 2020Review
- mTOR and other effector kinase signals that impact T cell function and activity.Immunological reviews · 2019Review
- RasGRP1 is a potential biomarker to stratify anti-EGFR therapy response in colorectal cancer.JCI insight · 2019Article
- Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells.Cell reports · 2019Article
- Mevalonate Metabolism in Cancer Stemness and Trained Immunity.Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
Abstract
Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1(Anaef), with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1(Anaef) mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44(hi) Helios(+) PD-1(+) CD4(+) T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1(Anaef) is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1(Anaef) naïve CD4(+) T cells. CD44 expression, CD4(+) T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1(Anaef)Mtor(chino) double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1(Anaef) T cell dysregulation. DOI: http://dx.doi.org/10.7554/eLife.01020.001.
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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.