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(Circulation Research. 2008;103:467.)
© 2008 American Heart Association, Inc.

Molecular Medicine

Interferon-, a Th1 Cytokine, Regulates Fat Inflammation

A Role for Adaptive Immunity in Obesity

Viviane Zorzanelli Rocha, Eduardo J. Folco, Galina Sukhova, Koichi Shimizu, Israel Gotsman, Ashley H. Vernon, Peter Libby

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.

Correspondence to Peter Libby, MD, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, 02115. 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-A^b, 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 IFN-inducible protein-10 and I-A^b, 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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