ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation.
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.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- WGCNA and molecular docking identify hub genes for cardiac aging.Frontiers in cardiovascular medicine · 2023Article
- Upregulated Expression of IL2RB Causes Disorder of Immune Microenvironment in Patients with Kawasaki Disease.BioMed research international · 2022Article
- Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma.The Journal of international medical research · 2021Article
- A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8Scientific reports · 2021Article
- Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects.The Journal of experimental medicine · 2021Article
- The Clinical Aspect of Adaptor Molecules in T Cell Signaling: Lessons Learnt From Inborn Errors of Immunity.Frontiers in immunology · 2021Review
- Development and Validation of a Prognostic Gene Signature Correlated With M2 Macrophage Infiltration in Esophageal Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
- Effect of Grilled Nux Vomica on Differential RNA Expression Profile of Gastrocnemius Muscle and Toll‑Like Receptor 4 (TLR-4)/Nuclear Factor kappa B (NF-κB) Signaling in Experimental Autoimmune Myasthenia Gravis Rats.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Identification of Key Genes and Potential New Biomarkers for Ovarian Aging: A Study Based on RNA-Sequencing Data.Frontiers in genetics · 2020Article
- Article
- Novel Insights reveal Anti-microbial Gene Regulation of Piglet Intestine Immune in response to Clostridium perfringens Infection.Scientific reports · 2019Article
- Phenotypic Expansion in Nasu-Hakola Disease: Immunological Findings in Three Patients and Proposal of a Unifying Pathogenic Hypothesis.Frontiers in immunology · 2019Article
- Article
- Identification of hub genes and regulatory factors of glioblastoma multiforme subgroups by RNA-seq data analysis.International journal of molecular medicine · 2016Article
- A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation.PLoS genetics · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Gene variants that disrupt TCR signaling can cause severe immune deficiency, yet less disruptive variants are sometimes associated with immune pathology. Null mutations of the gene encoding the scaffold protein Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76), for example, cause an arrest of T cell positive selection, whereas a synthetic membrane-targeted allele allows limited positive selection but is associated with proinflammatory cytokine production and autoantibodies. Whether these and other enigmatic outcomes are due to a biochemical uncoupling of tolerogenic signaling, or simply a quantitative reduction of protein activity, remains to be determined. In this study we describe a splice variant of Lcp2 that reduced the amount of wild-type SLP-76 protein by ~90%, disrupting immunogenic and tolerogenic pathways to different degrees. Mutant mice produced excessive amounts of proinflammatory cytokines, autoantibodies, and IgE, revealing that simple quantitative reductions of SLP-76 were sufficient to trigger immune dysregulation. This allele reveals a dose-sensitive threshold for SLP-76 in the balance of immunity and immune dysregulation, a common disturbance of atypical clinical immune deficiencies.
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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.