title: Defective leptin/leptin receptor signaling improves regulatory T cell immune response and protects mice from atherosclerosis.
abstract: OBJECTIVE
  Obesity is a major risk factor for atherosclerosis and is associated with increased cardiovascular morbidity and mortality. However, the precise molecular pathways responsible for this close association remain poorly understood.
  
  
  RESULTS
  In this study, we report that leptin-deficiency (ob/ob) in low-density lipoprotein receptor knockout (ldlr(-/-)) mice induces an unexpected 2.2- to 6-fold reduction in atherosclerotic lesion development, compared with ldlr(-/-) mice having similar total cholesterol levels. Ldlr(-/-)/ob/ob mice show reduced T cell helper type 1 (Th1) response, enhanced expression of Foxp3, the specification transcription factor of regulatory T (Treg) cells, and improved Treg cell function. Leptin receptor-deficient (db/db) mice display marked increase in the number and suppressive function of Treg cells. Supplementation of Treg-deficient lymphocytes with Treg cells from db/db mice in an experimental model of atherosclerosis induces a significant reduction of lesion size and a marked inhibition of interferon (INF)-gamma production, compared with supplementation by Treg cells from wild-type mice.
  
  
  CONCLUSIONS
  These results identify a critical role for leptin/leptin receptor pathway in the modulation of the regulatory immune response in atherosclerosis, and suggest that alteration in regulatory immunity may predispose obese individuals to atherosclerosis.
authors: Institut National de la Sante et de la Recherche Medicale, U689, 41 Bd de la Chapelle, Paris, France.
authors: Soraya
authors: S
authors: Taleb
authors: Olivier
authors: O
authors: Herbin
authors: Hafid
authors: H
authors: Ait-Oufella
authors: Wim
authors: W
authors: Verreth
authors: Pierre
authors: P
authors: Gourdy
authors: Véronique
authors: V
authors: Barateau
authors: Régine
authors: R
authors: Merval
authors: Bruno
authors: B
authors: Esposito
authors: Karine
authors: K
authors: Clément
authors: Paul
authors: P
authors: Holvoet
authors: Alain
authors: A
authors: Tedgui
authors: Ziad
authors: Z
authors: Mallat
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007111:Immunity, Cellular / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D018106:CD28 Antigens; D004041:Dietary Fats; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020738:Leptin; D008055:Lipids; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D007371:Interferon-gamma