Published online before print July 24, 2008, doi: 10.1161/CIRCRESAHA.108.177105
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Submitted on April 9, 2008
Revised on July 9, 2008
Accepted on July 15, 2008
Interferon-
, a Th1 Cytokine, Regulates Fat Inflammation. A Role for Adaptive Immunity in Obesity
Viviane Zorzanelli Rocha ;
From the Cardiovascular Division (V.Z.R., E.J.F., G.S., K.S., P.L.), and Division of General and Gastrointestinal Surgery (A.H.V.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; and Heart Institute (I.G.), Hadassah University Hospital, Jerusalem, Israel.
* To whom correspondence should be addressed. E-mail: plibby{at}rics.bwh.harvard.edu.
Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher numbers of both CD4+ and CD8+ T cells than lean controls, monitored by flow cytometry. When stimulated in vitro, T cells from obese AT produced more interferon (IFN)
than those from controls. AT from obese animals also had more cells expressing I-Ab, a mouse class II histocompatibility marker implicated in antigen presentation, as determined by immunostaining. Differentiated 3T3-L1 cells stimulated with recombinant IFN or T-helper 1–derived supernatant produced several chemokines and their mRNAs. Obese IFN-deficient animals had significantly reduced AT expression of mRNA-encoding inflammatory genes such as tumor necrosis factor-
and monocyte chemoattractant protein-1, decreased AT inflammatory cell accumulation, and better glucose tolerance than control animals consuming the same diet. Obese mice doubly deficient for IFN receptor and apolipoprotein (Apo)E on a mixed 129SvEv/C57BL/6 (129/B6) genetic background, despite exhibiting similar AT mRNA levels of tumor necrosis factor- and monocyte chemoattractant protein-1 as 129/B6-ApoE-/- controls, had decreased expression of important T cell–related genes, such as IP-10 (IFN-inducible protein-10) and I-Ab, and lower plasma triglycerides and glucose. These results indicate a role for T cells and IFN, a prototypical T-helper 1 cytokine, in regulation of the inflammatory response that accompanies obesity.
Key words: inflammation • obesity • adipose tissue • T cell • IFN
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