ArticleProceedings of the National Academy of Sciences of the United States of America2012
Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 138 citations in OpenAlex.
- Regulatory B cells: heterogeneity, immunosuppressive networks, and contributions to autoimmune pathogenesis.Frontiers in immunology · 2026Review
- Inhibiting B cells enhances the efficacy of STING agonism or immune checkpoint blockade in hepatocellular carcinoma.Nature communications · 2025Article
- Efferocytosis: the art of cellular clearance and novel perspectives in disease therapy.Molecular cancer · 2025Review
- Heterogeneity of regulatory B cells in autoimmune diseases: implications for immune equilibrium and therapeutic strategies.Immunotherapy advances · 2025Review
- Immunosuppressive cells in acute myeloid leukemia: mechanisms and therapeutic target.Frontiers in immunology · 2025Review
- The Role of Regulatory B Lymphocytes in Allergic Diseases.Biomedicines · 2024Review
- The ability of human TIM1 to bind phosphatidylethanolamine enhances viral uptake and efferocytosis compared to rhesus and mouse orthologs.Journal of virology · 2024Article
- Directed protein engineering identifies a human TIM-4 blocking antibody that enhances anti-tumor response to checkpoint inhibition in murine colon carcinoma.Antibody therapeutics · 2024Article
- The ability of human TIM1 to bind phosphatidylethanolamine enhances viral uptake and efferocytosis compared to rhesus and mouse orthologs.bioRxiv : the preprint server for biology · 2024Article
- Review
- Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis.Frontiers in immunology · 2024Article
- IFNγ-Producing B Cells Play a Regulating Role in Infection-Mediated Inhibition of Allergy.Biology · 2023Article
- Article
- Ex vivo-expanded human CD19Nature communications · 2022Article
- Efferocytosis in multisystem diseases (Review).Molecular medicine reports · 2022Review
- Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition).European journal of immunology · 2021Review
- Sexual Dimorphism in Outcomes of Non-muscle-invasive Bladder Cancer: A Role of CD163+ Macrophages, B cells, and PD-L1 Immune Checkpoint.European urology open science · 2021Article
- KIM-1 mediates fatty acid uptake by renal tubular cells to promote progressive diabetic kidney disease.Cell metabolism · 2021Article
- Regulatory B cells in cancer.Immunological reviews · 2021Review
- Altered Tim-1 and IL-10 Expression in Regulatory B Cell Subsets in Type 1 Diabetes.Frontiers in immunology · 2021Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Tim-1, a type I transmembrane glycoprotein, consists of an IgV domain and a mucin domain. The IgV domain is essential for binding Tim-1 to its ligands, but little is known about the role of the mucin domain, even though genetic association of TIM-1 with atopy/asthma has been linked to the length of mucin domain. We generated a Tim-1-mutant mouse (Tim-1(Δmucin)) in which the mucin domain was deleted genetically. The mutant mice showed a profound defect in IL-10 production from regulatory B cells (Bregs). Associated with the loss of IL-10 production in B cells, older Tim-1(Δmucin) mice developed spontaneous autoimmunity associated with hyperactive T cells, with increased production of IFN-γ and elevated serum levels of Ig and autoantibodies. However, Tim-1(Δmucin) mice did not develop frank systemic autoimmune disease unless they were crossed onto the Fas-mutant lpr mice on a C57BL/6 background. Tim-1(Δmucin)lpr mice developed accelerated and fulminant systemic autoimmunity with accumulation of abnormal double-negative T cells and autoantibodies to a number of lupus-associated autoantigens. Thus, Tim-1 plays a critical role in maintaining suppressive Breg function, and our data also demonstrate an unexpected role of the Tim-1 mucin domain in regulating Breg function and maintaining self-tolerance.
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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.