ArticleThe Journal of experimental medicine2014
RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 10 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
185 citing papers in PubMed, 10 syntheses or guidelines pooled it, 322 citations in OpenAlex.
- The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Pooled it
- Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- The efficacy and safety of neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer patients: a systematic review.Frontiers in immunology · 2024Pooled it
- The efficacy and safety of immunotherapy as first-line treatment for extensive-stage small cell lung cancer: evaluating based on reconstructed individual patient data.Frontiers in oncology · 2024Pooled it
- Immune-related adverse events associated with nab-paclitaxel/paclitaxel combined with immune checkpoint inhibitors: a systematic review and network meta-analysis.Frontiers in immunology · 2023Pooled it
- Immune-Related Pneumonitis Was Decreased by Addition of Chemotherapy with PD-1/L1 Inhibitors: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials (RCTs).Current oncology (Toronto, Ont.) · 2022Pooled it
- Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer.Frontiers in immunology · 2022Pooled it
- Safety and Efficacy of Anti-PD-1 Monoclonal Antibodies in Patients With Relapsed or Refractory Lymphoma: A Meta-Analysis of Prospective Clinic Trails.Frontiers in pharmacology · 2019Pooled it
- Risk of Pneumonitis and Pneumonia Associated With Immune Checkpoint Inhibitors for Solid Tumors: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2019Pooled it
- Discovery of common and rare genetic risk variants for colorectal cancer.Nature genetics · 2019Pooled it
- PD-L1Haematologica · 2018Trial
- Incidence of and risk factors for immune checkpoint inhibitor-related pneumonitis in thoracic malignancies: a prospective multicenter study.The oncologist · 2026Observational
- Dendritic cell PD-L2 restrains intratumoral CD8bioRxiv : the preprint server for biology · 2026Article
- Atlas of glomerular disease-specific genetic effects on blood transcriptome.medRxiv : the preprint server for health sciences · 2026Article
- PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.Nature reviews. Rheumatology · 2026Review
- Article
- Does immunotherapy hold great promise in endometrial cancer care?Frontiers in immunology · 2026Review
- Article
- Anti-PD-L2 immunotherapy is efficacious against melanoma in aged hosts through IL-17 and IFNγ signalling.Nature communications · 2025Article
- Emerging Issues Regarding the Effects of the Microbiome on Lung Cancer Immunotherapy.Biomolecules · 2025Review
125 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
We report that programmed death ligand 2 (PD-L2), a known ligand of PD-1, also binds to repulsive guidance molecule b (RGMb), which was originally identified in the nervous system as a co-receptor for bone morphogenetic proteins (BMPs). PD-L2 and BMP-2/4 bind to distinct sites on RGMb. Normal resting lung interstitial macrophages and alveolar epithelial cells express high levels of RGMb mRNA, whereas lung dendritic cells express PD-L2. Blockade of the RGMb-PD-L2 interaction markedly impaired the development of respiratory tolerance by interfering with the initial T cell expansion required for respiratory tolerance. Experiments with PD-L2-deficient mice showed that PD-L2 expression on non-T cells was critical for respiratory tolerance, but expression on T cells was not required. Because PD-L2 binds to both PD-1, which inhibits antitumor immunity, and to RGMb, which regulates respiratory immunity, targeting the PD-L2 pathway has therapeutic potential for asthma, cancer, and other immune-mediated disorders. Understanding this pathway may provide insights into how to optimally modulate the PD-1 pathway in cancer immunotherapy while minimizing adverse events.
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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.