T-Cell Costimulation Protects Obesity-Induced Adipose Inflammation and Insulin Resistance
- Jixin Zhong1,
- Xiaoquan Rao1,
- Zachary Braunstein2,
- Anne Taylor3,
- Vimal Narula3,
- Jeffrey Hazey3,
- Dean Mikami3,
- Bradley Needleman3,
- Jessica Rutsky2,
- Qinghua Sun2,
- Jeffrey A. Deiuliis1,
- Abhay R. Satoskar4 and
- Sanjay Rajagopalan1⇑
- 1Division of Cardiology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
- 2Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
- 3Department of Surgery, The Ohio State University, Columbus, OH
- 4Division of Experimental Pathology, The Ohio State University, Columbus, OH
- Corresponding author: Sanjay Rajagopalan, .
A key pathophysiologic role for activated T-cells in mediating adipose inflammation and insulin resistance (IR) has been recently postulated. However, mechanisms underlying their activation are poorly understood. In this study, we demonstrated a previously unrecognized homeostatic role for the costimulatory B7 molecules (CD80 and CD86) in preventing adipose inflammation. Instead of promoting inflammation, which was found in many other disease conditions, B7 costimulation reduced adipose inflammation by maintaining regulatory T-cell (Treg) numbers in adipose tissue. In both humans and mice, expression of CD80 and CD86 was negatively correlated with the degree of IR and adipose tissue macrophage infiltration. Decreased B7 expression in obesity appeared to directly impair Treg proliferation and function that lead to excessive proinflammatory macrophages and the development of IR. CD80/CD86 double knockout (B7 KO) mice had enhanced adipose macrophage inflammation and IR under both high-fat and normal diet conditions, accompanied by reduced Treg development and proliferation. Adoptive transfer of Tregs reversed IR and adipose inflammation in B7 KO mice. Our results suggest an essential role for B7 in maintaining Tregs and adipose homeostasis and may have important implications for therapies that target costimulation in type 2 diabetes.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1094/-/DC1.
See accompanying article, p. 1179.
- Received July 12, 2013.
- Accepted November 8, 2013.
- © 2014 by the American Diabetes Association.
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