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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7210
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pubmed:dateCreated |
2008-9-16
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pubmed:databankReference |
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pubmed:abstractText |
Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins. It is induced in activated T cells and is reported to process a variety of substrates including the anti-inflammatory cytokine transforming growth factor (TGF)-beta1 (refs 2-4), but the non-redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T-cell development but impaired the function of regulatory and effector T cells, which produced less TGF-beta1. Furin-deficient T regulatory (Treg) cells were less protective in a T-cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin-deficient effector cells were inherently over-active and were resistant to suppressive activity of wild-type Treg cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non-redundant, essential function in regulating TGF-beta1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-10352281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-11141505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-12360192,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-12482908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-12832286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-14676299,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-14707053,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-15471862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-15630140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-16167351,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-16244650,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-16627761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-17481928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-17525753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-17537721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-17620362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-17694047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-17948127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-18064302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-7908916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-8676088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-9670041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18701887-9811571
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1476-4687
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pubmed:author |
pubmed-author:AnderssonJohnJ,
pubmed-author:BelkaidYasmineY,
pubmed-author:BouladouxNicolasN,
pubmed-author:CreemersJohnJ,
pubmed-author:FussIvanI,
pubmed-author:O'SheaJohn JJJ,
pubmed-author:PesuMarkoM,
pubmed-author:QuezadoMarthaM,
pubmed-author:RoebroekAntonA,
pubmed-author:ShevachEthan MEM,
pubmed-author:StroberWarrenW,
pubmed-author:WatfordWendy TWT,
pubmed-author:WeiLaiL,
pubmed-author:XuLiliL
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
455
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
246-50
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pubmed:dateRevised |
2011-9-28
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pubmed:meshHeading |
pubmed-meshheading:18701887-Animals,
pubmed-meshheading:18701887-Antigens, CD,
pubmed-meshheading:18701887-Antigens, CD4,
pubmed-meshheading:18701887-Autoimmunity,
pubmed-meshheading:18701887-Colitis,
pubmed-meshheading:18701887-Furin,
pubmed-meshheading:18701887-Gene Expression Profiling,
pubmed-meshheading:18701887-Immune Tolerance,
pubmed-meshheading:18701887-Immunologic Memory,
pubmed-meshheading:18701887-Integrin alpha Chains,
pubmed-meshheading:18701887-Lymphocyte Activation,
pubmed-meshheading:18701887-Mice,
pubmed-meshheading:18701887-Mice, Inbred C57BL,
pubmed-meshheading:18701887-T-Lymphocytes,
pubmed-meshheading:18701887-Thymus Gland,
pubmed-meshheading:18701887-Transforming Growth Factor beta1
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pubmed:year |
2008
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pubmed:articleTitle |
T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance.
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pubmed:affiliation |
Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. pesum@mail.nih.gov
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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