ArticleThe Journal of biological chemistry2020
Leukocyte-associated immunoglobulin-like receptor 1 inhibits T-cell signaling by decreasing protein phosphorylation in the T-cell signaling pathway.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Expanded CD16Scientific reports · 2025Article
- Inhibitory pattern recognition receptors: lessons from LAIR1.Nature reviews. Immunology · 2025Review
- Collagen in pituitary adenomas: A comprehensive review of biological roles and clinical implications.Journal of clinical & translational endocrinology · 2025Review
- NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR.Scientific reports · 2025Article
- The Role of LAIR1 as a Regulatory Receptor of Antitumor Immune Cell Responses and Tumor Cell Growth and Expansion.Biomolecules · 2025Review
- Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.Clinical and translational medicine · 2025Review
- Transcriptomics-Based Study of Immune Genes Associated with Subclinical Mastitis in Bactrian Camels.Veterinary sciences · 2025Article
- Human T-cell lymphotropic virus type 1 (HTLV-1) grip on T-cells: investigating the viral tapestry of activation.Infectious agents and cancer · 2024Article
- LAIR-1 limits macrophage activation in acute inflammatory lung injury.Mucosal immunology · 2023Article
- Novel PD-L1- and collagen-expressing patient-derived cell line of undifferentiated pleomorphic sarcoma (JBT19) as a model for cancer immunotherapy.Scientific reports · 2023Article
- Immune checkpoints in rheumatoid arthritis: progress and promise.Frontiers in immunology · 2023Review
- LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms.International journal of molecular sciences · 2022Review
- Role of Citrullinated Collagen in Autoimmune Arthritis.International journal of molecular sciences · 2022Article
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity.The Journal of allergy and clinical immunology · 2022Article
- An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis.Frontiers in pharmacology · 2022Article
- Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets.Virus research · 2021Review
- Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking human LAIR-collagen interaction.eLife · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Multiple observations implicate T-cell dysregulation as a central event in the pathogenesis of rheumatoid arthritis. Here, we investigated mechanisms for suppressing T-cell activation via the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1). To determine how LAIR-1 affects T-cell receptor (TCR) signaling, we compared 1) T cells from LAIR-1-sufficient and -deficient mice, 2) Jurkat cells expressing either LAIR-1 mutants or C-terminal Src kinase (CSK) mutants, and 3) T cells from mice that contain a CSK transgene susceptible to chemical inhibition. Our results indicated that LAIR-1 engagement by collagen or by complement C1q (C1Q, which contains a collagen-like domain) inhibits TCR signaling by decreasing the phosphorylation of key components in the canonical T-cell signaling pathway, including LCK proto-oncogene SRC family tyrosine kinase (LCK), LYN proto-oncogene SRC family tyrosine kinase (LYN), ζ chain of T-cell receptor-associated protein kinase 70 (ZAP-70), and three mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase 1/2, and p38). The intracellular region of LAIR-1 contains two immunoreceptor tyrosine-based inhibition motifs that are both phosphorylated by LAIR-1 activation, and immunoprecipitation experiments revealed that Tyr-251 in LAIR-1 binds CSK. Using CRISPR/Cas9-mediated genome editing, we demonstrate that CSK is essential for the LAIR-1-induced inhibition of the human TCR signal transduction. T cells from mice that expressed a PP1 analog-sensitive form of CSK (CskAS) corroborated these findings, and we also found that Tyr-251 is critical for LAIR-1's inhibitory function. We propose that LAIR-1 activation may be a strategy for controlling inflammation and may offer a potential therapeutic approach for managing autoimmune diseases.
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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.