ArticleThe Journal of allergy and clinical immunology2022
LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity.
Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 37 citations in OpenAlex.
- MyD88 mediates allergic airway inflammation by regulating ILC2s function through inducing the formation of P38/GATA3 complex.Respiratory research · 2026Article
- ILC2s and their immune checkpoints in the antitumor response.Journal for immunotherapy of cancer · 2026Review
- Melatonin suppresses ILC2-driven airway hyperreactivity via glutathione-dependent metabolic reprogramming.Frontiers in immunology · 2026Article
- Mast cell driven immunometabolism as a therapeutic entry point in ESCC.Frontiers in cell and developmental biology · 2026Review
- The Expanding Role of ILC2s in Allergic Airways Disease.Allergy · 2026Review
- Macrophages regulate PD-1 and CTLA-4 expression on ILC2s and their responsiveness in the tumor microenvironment.Cellular & molecular immunology · 2025Article
- Intraepithelial Lymphocytes and LAIR1 Expression in Celiac Disease.Biomedicines · 2025Article
- Inhibitory pattern recognition receptors: lessons from LAIR1.Nature reviews. Immunology · 2025Review
- The immunology of asthma.Nature immunology · 2025Review
- Genome-Wide Aggregated Trans Effects Analysis Identifies Genes Encoding Immune Checkpoints as Core Genes for Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- The Role of LAIR1 as a Regulatory Receptor of Antitumor Immune Cell Responses and Tumor Cell Growth and Expansion.Biomolecules · 2025Review
- Update on type 2 immunity.The Journal of allergy and clinical immunology · 2025Review
- Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?Neuro-oncology · 2025Review
- Adaptive immune cells antagonize ILC2 homeostasis via SLAMF3 and SLAMF5.Science advances · 2025Article
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer.Oncology letters · 2025Article
- SIRPα engagement regulates ILC2 effector function and alleviates airway hyperreactivity via modulating energy metabolism.Cellular & molecular immunology · 2024Article
- Airways epithelial exposure to Streptococcus pneumoniae in the presence of the alarmin IL-33 induces a novel subset of pro-inflammatory ILC2s promoting a mixed inflammatory response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Bronchial epithelial transcriptomics and experimental validation reveal asthma severity-related neutrophilc signatures and potential treatments.Communications biology · 2024Article
- LAIR-1 limits macrophage activation in acute inflammatory lung injury.Mucosal immunology · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundType 2 innate lymphoid cells (ILC2s) are relevant players in type 2 asthma. They initiate eosinophil infiltration and airway hyperreactivity (AHR) through cytokine secretion. Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor considered to be an immune checkpoint in different inflammatory diseases.
objectiveOur aim here was to investigate the expression of LAIR-1 and assess its role in human and murine ILC2s.
methodsWild-type and LAIR-1 knockout mice were intranasally challenged with IL-33, and pulmonary ILC2s were sorted to perform an ex vivo comparative study based on RNA sequencing and flow cytometry. We next studied the impact of LAIR-1 deficiency on AHR and lung inflammation by using knockout mice and adoptive transfer experiments in Rag2
resultsWe have demonstrated that LAIR-1 is inducible on activated ILC2s and downregulates cytokine secretion and effector function. LAIR-1 signaling in ILC2s was mediated via inhibitory pathways, including SHP1/PI3K/AKT, and LAIR-1 deficiency led to exacerbated ILC2-dependent AHR in IL-33 and Alternaria alternata models. In adoptive transfer experiments, we confirmed the LAIR-1-mediated regulation of ILC2s in vivo. Interestingly, LAIR-1 was expressed and inducible in human ILC2s, and knockdown approaches of Lair1 resulted in higher cytokine production. Finally, engagement of LAIR-1 by physiologic ligand C1q significantly reduced ILC2-dependent AHR in a humanized ILC2 murine model.
conclusionOur results unravel a novel regulatory axis in ILC2s with the capacity to reduce allergic AHR and lung inflammation.
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