pubmed-article:19633657 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:19633657 | lifeskim:mentions | umls-concept:C0021083 | lld:lifeskim |
pubmed-article:19633657 | lifeskim:mentions | umls-concept:C0021655 | lld:lifeskim |
pubmed-article:19633657 | lifeskim:mentions | umls-concept:C1882115 | lld:lifeskim |
pubmed-article:19633657 | pubmed:issue | 8 | lld:pubmed |
pubmed-article:19633657 | pubmed:dateCreated | 2009-8-7 | lld:pubmed |
pubmed-article:19633657 | pubmed:abstractText | Obesity and its associated metabolic syndromes represent a growing global challenge, yet mechanistic understanding of this pathology and current therapeutics are unsatisfactory. We discovered that CD4(+) T lymphocytes, resident in visceral adipose tissue (VAT), control insulin resistance in mice with diet-induced obesity (DIO). Analyses of human tissue suggest that a similar process may also occur in humans. DIO VAT-associated T cells show severely biased T cell receptor V(alpha) repertoires, suggesting antigen-specific expansion. CD4(+) T lymphocyte control of glucose homeostasis is compromised in DIO progression, when VAT accumulates pathogenic interferon-gamma (IFN-gamma)-secreting T helper type 1 (T(H)1) cells, overwhelming static numbers of T(H)2 (CD4(+)GATA-binding protein-3 (GATA-3)(+)) and regulatory forkhead box P3 (Foxp3)(+) T cells. CD4(+) (but not CD8(+)) T cell transfer into lymphocyte-free Rag1-null DIO mice reversed weight gain and insulin resistance, predominantly through T(H)2 cells. In obese WT and ob/ob (leptin-deficient) mice, brief treatment with CD3-specific antibody or its F(ab')(2) fragment, reduces the predominance of T(H)1 cells over Foxp3(+) cells, reversing insulin resistance for months, despite continuation of a high-fat diet. Our data suggest that the progression of obesity-associated metabolic abnormalities is under the pathophysiological control of CD4(+) T cells. The eventual failure of this control, with expanding adiposity and pathogenic VAT T cells, can successfully be reversed by immunotherapy. | lld:pubmed |
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pubmed-article:19633657 | pubmed:language | eng | lld:pubmed |
pubmed-article:19633657 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19633657 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:19633657 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:19633657 | pubmed:month | Aug | lld:pubmed |
pubmed-article:19633657 | pubmed:issn | 1546-170X | lld:pubmed |
pubmed-article:19633657 | pubmed:author | pubmed-author:DruckerDaniel... | lld:pubmed |
pubmed-article:19633657 | pubmed:author | pubmed-author:WinerShawnS | lld:pubmed |
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pubmed-article:19633657 | pubmed:author | pubmed-author:TsuiHubertH | lld:pubmed |
pubmed-article:19633657 | pubmed:author | pubmed-author:WinerDanielD | lld:pubmed |
pubmed-article:19633657 | pubmed:author | pubmed-author:MaezawaYukoY | lld:pubmed |
pubmed-article:19633657 | pubmed:author | pubmed-author:EnglemanEdgar... | lld:pubmed |
pubmed-article:19633657 | pubmed:author | pubmed-author:WangYongqianY | lld:pubmed |
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pubmed-article:19633657 | pubmed:author | pubmed-author:ChanYinY | lld:pubmed |
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pubmed-article:19633657 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:19633657 | pubmed:volume | 15 | lld:pubmed |
pubmed-article:19633657 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:19633657 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:19633657 | pubmed:pagination | 921-9 | lld:pubmed |
pubmed-article:19633657 | pubmed:dateRevised | 2011-7-27 | lld:pubmed |
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pubmed-article:19633657 | pubmed:year | 2009 | lld:pubmed |
pubmed-article:19633657 | pubmed:articleTitle | Normalization of obesity-associated insulin resistance through immunotherapy. | lld:pubmed |
pubmed-article:19633657 | pubmed:affiliation | Department of Pediatrics & Immunology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. | lld:pubmed |
pubmed-article:19633657 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:19633657 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
pubmed-article:19633657 | pubmed:publicationType | Evaluation Studies | lld:pubmed |
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