ArticleBlood2008
Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05695521 (Phase 1 Safety Run-in Study and Phase 1b Randomized, Double Blinded, Placebo Controlled Trial), which is not on this map. Cited by 36 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.
Phase 1 Safety Run-in Study and Phase 1b Randomized, Double Blinded, Placebo Controlled Trial
Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- A CRISPR screen targeting PI3K effectors identifies RASA3 as a negative regulator of LFA-1-mediated adhesion in T cells.Science signaling · 2022Article
- The Roles of Neutrophils Linking Periodontitis and Atherosclerotic Cardiovascular Diseases.Frontiers in immunology · 2022Review
- Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality.ESC heart failure · 2021Article
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-1.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Del-1, an Endogenous Inhibitor of TGF-β Activation, Attenuates Fibrosis.Frontiers in immunology · 2020Article
- E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease.Frontiers in cardiovascular medicine · 2020Review
- Deficiency of the T cell regulator Casitas B-cell lymphoma-B aggravates atherosclerosis by inducing CD8+ T cell-mediated macrophage death.European heart journal · 2019Article
- DEL-1 promotes macrophage efferocytosis and clearance of inflammation.Nature immunology · 2019Article
- Sophora flavescens protects against mycobacterial Trehalose Dimycolate-induced lung granuloma by inhibiting inflammation and infiltration of macrophages.Scientific reports · 2018Article
- Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche.The Journal of clinical investigation · 2017Article
- Endogenous developmental endothelial locus-1 limits ischaemia-related angiogenesis by blocking inflammation.Thrombosis and haemostasis · 2017Article
- A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity.Nature immunology · 2017Article
- Article
- E3 ubiquitin ligase Cbl-b negatively regulates C-type lectin receptor-mediated antifungal innate immunity.The Journal of experimental medicine · 2016Article
- Adipocyte-Specific Hypoxia-Inducible Factor 2α Deficiency Exacerbates Obesity-Induced Brown Adipose Tissue Dysfunction and Metabolic Dysregulation.Molecular and cellular biology · 2016Article
- Proteome Based Construction of the Lymphocyte Function-Associated Antigen 1 (LFA-1) Interactome in Human Dendritic Cells.PloS one · 2016Article
- Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease.Nature medicine · 2015Article
- Leukocyte integrins: role in leukocyte recruitment and as therapeutic targets in inflammatory disease.Pharmacology & therapeutics · 2015Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Inside-out signaling regulation of the beta2-integrin leukocyte function-associated antigen-1 (LFA-1) by different cytoplasmic proteins, including 14-3-3 proteins, is essential for adhesion and migration of immune cells. Here, we identify a new pathway for the regulation of LFA-1 activity by Cbl-b, an adapter molecule and ubiquitin ligase that modulates several signaling pathways. Cbl-b-/- mice displayed increased macrophage recruitment in thioglycollate-induced peritonitis, which was attributed to Cbl-b deficiency in macrophages, as assessed by bone marrow chimera experiments. In vitro, Cbl-b-/- bone marrow-derived mononuclear phagocytes (BMDMs) displayed increased adhesion to endothelial cells. Activation of LFA-1 in Cbl-b-deficient cells was responsible for their increased endothelial adhesion in vitro and peritoneal recruitment in vivo, as the phenotype of Cbl-b deficiency was reversed in Cbl-b-/-LFA-1-/- mice. Consistently, LFA-1-mediated adhesion of BMDM to ICAM-1 but not VLA-4-mediated adhesion to VCAM-1 was enhanced by Cbl-b deficiency. Cbl-b deficiency resulted in increased phosphorylation of T758 in the beta2-chain of LFA-1 and thereby in enhanced association of 14-3-3beta protein with the beta2-chain, leading to activation of LFA-1. Consistently, disruption of the 14-3-3/beta2-integrin interaction abrogated the enhanced ICAM-1 adhesion of Cbl-b-/- BMDMs. In conclusion, Cbl-b deficiency activates LFA-1 and LFA-1-mediated inflammatory cell recruitment by stimulating the interaction between the LFA-1 beta-chain and 14-3-3 proteins.
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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.