| Tim-1 stimulation of dendritic cells regulates the balance between effector and regulatory T cells. | |
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MedLine Citation:
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PMID: 21469101 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We show that the T-cell immunoglobalin mucin, Tim-1, initially reported to be expressed on CD4(+) T cells, is constitutively expressed on dendritic cells (DCs) and that its expression further increases after DC maturation. Tim-1 signaling into DCs upregulates costimulatory molecule expression and proinflammatory cytokine production, thereby promoting effector T-cell responses, while inhibiting Foxp3(+) Treg responses. By contrast, Tim-1 signaling in T cells only regulates Th2 responses. Using a high-avidity/agonistic anti-Tim-1 antibody as a co-adjuvant enhances the immunogenic function of DCs, decreases the suppressive function of Tregs, and substantially increases proinflammatory Th17 responses in vivo. The treatment with high- but not low-avidity anti-Tim-1 not only worsens experimental autoimmune encephalomyelitis (EAE) in susceptible mice but also breaks tolerance and induces EAE in a genetically resistant strain of mice. These findings indicate that Tim-1 has an important role in regulating DC function and thus shifts the balance between effector and regulatory T cells towards an enhanced immune response. By understanding the mechanisms by which Tim-1 regulates DC and T-cell responses, we may clarify the potential utility of Tim-1 as a target of therapy against autoimmunity, cancer, and infectious diseases. |
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Authors:
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Sheng Xiao; Bing Zhu; Hulin Jin; Chen Zhu; Dale T Umetsu; Rosemarie H DeKruyff; Vijay K Kuchroo |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-05-25 |
Journal Detail:
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Title: European journal of immunology Volume: 41 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-27 Completed Date: 2011-08-23 Revised Date: 2011-11-11 |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 1539-49 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / metabolism Cells, Cultured Dendritic Cells / immunology, metabolism*, pathology Encephalomyelitis, Autoimmune, Experimental / immunology* Forkhead Transcription Factors / genetics, metabolism Immunization Interleukin-17 / genetics, metabolism Lymphocyte Activation Membrane Proteins / immunology, metabolism* Mice Mice, Transgenic Myelin Proteolipid Protein / immunology Peptide Fragments / immunology Receptors, Antigen, T-Cell, alpha-beta / genetics Signal Transduction / immunology T-Lymphocyte Subsets / immunology, metabolism*, pathology T-Lymphocytes, Regulatory / immunology, metabolism*, pathology Th1-Th2 Balance |
| Grant Support | |
ID/Acronym/Agency:
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K01 DK090105-01/DK/NIDDK NIH HHS; K01 DK090105-02/DK/NIDDK NIH HHS; K01DK090105/DK/NIDDK NIH HHS; P01 AI039671-11/AI/NIAID NIH HHS; P01 AI039671-12/AI/NIAID NIH HHS; P01 AI039671-13/AI/NIAID NIH HHS; P01 AI039671-14/AI/NIAID NIH HHS; P01 AI039671-15/AI/NIAID NIH HHS; P01 AI039671-16/AI/NIAID NIH HHS; P01 AI054456-07/AI/NIAID NIH HHS; P01 AI073748-04/AI/NIAID NIH HHS; P01AI039671/AI/NIAID NIH HHS; P01AI054456/AI/NIAID NIH HHS; P01AI073748/AI/NIAID NIH HHS; P01NS038037/NS/NINDS NIH HHS; R01 AI044880-08/AI/NIAID NIH HHS; R01 AI044880-09/AI/NIAID NIH HHS; R01 NS035685-09/NS/NINDS NIH HHS; R01 NS035685-11/NS/NINDS NIH HHS; R01 NS035685-12/NS/NINDS NIH HHS; R01 NS035685-13/NS/NINDS NIH HHS; R01 NS035685-14/NS/NINDS NIH HHS; R01 NS045937-08/NS/NINDS NIH HHS; R01 NS045937-09/NS/NINDS NIH HHS; R01AI044880/AI/NIAID NIH HHS; R01HL069507/HL/NHLBI NIH HHS; R01NS035685/NS/NINDS NIH HHS; R01NS045937/NS/NINDS NIH HHS; R37 NS030843-11/NS/NINDS NIH HHS; R37 NS030843-12/NS/NINDS NIH HHS; R37 NS030843-13/NS/NINDS NIH HHS; R37 NS030843-14/NS/NINDS NIH HHS; R37 NS030843-15/NS/NINDS NIH HHS; R37 NS030843-16/NS/NINDS NIH HHS; R37 NS030843-17/NS/NINDS NIH HHS; R37NS030843/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Havcr1 protein, mouse; 0/Interleukin-17; 0/Membrane Proteins; 0/Myelin Proteolipid Protein; 0/Peptide Fragments; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/myelin proteolipid protein (139-151) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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