T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance

Jixin Zhong, Xiaoquan Rao, Zachary Braunstein, Anne Taylor, Vimal Narula, Jeffrey Hazey, Dean Mikami, Bradley Needleman, Jessica Rutsky, Qinghua Sun, Jeffrey A. Deiuliis, Abhay R. Satoskar, Sanjay Rajagopalan

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1289-1302
Number of pages14
JournalDiabetes
Volume63
Issue number4
DOIs
StatePublished - Apr 1 2014
Externally publishedYes

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Insulin Resistance
Obesity
Inflammation
T-Lymphocytes
Macrophages
Adipose Tissue
B7 Antigens
Adoptive Transfer
High Fat Diet
Regulatory T-Lymphocytes
Type 2 Diabetes Mellitus
Homeostasis
Cell Count
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Zhong, J., Rao, X., Braunstein, Z., Taylor, A., Narula, V., Hazey, J., ... Rajagopalan, S. (2014). T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance. Diabetes, 63(4), 1289-1302. https://doi.org/10.2337/db13-1094

T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance. / Zhong, Jixin; Rao, Xiaoquan; Braunstein, Zachary; Taylor, Anne; Narula, Vimal; Hazey, Jeffrey; Mikami, Dean; Needleman, Bradley; Rutsky, Jessica; Sun, Qinghua; Deiuliis, Jeffrey A.; Satoskar, Abhay R.; Rajagopalan, Sanjay.

In: Diabetes, Vol. 63, No. 4, 01.04.2014, p. 1289-1302.

Research output: Contribution to journalArticle

Zhong, J, Rao, X, Braunstein, Z, Taylor, A, Narula, V, Hazey, J, Mikami, D, Needleman, B, Rutsky, J, Sun, Q, Deiuliis, JA, Satoskar, AR & Rajagopalan, S 2014, 'T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance', Diabetes, vol. 63, no. 4, pp. 1289-1302. https://doi.org/10.2337/db13-1094
Zhong, Jixin ; Rao, Xiaoquan ; Braunstein, Zachary ; Taylor, Anne ; Narula, Vimal ; Hazey, Jeffrey ; Mikami, Dean ; Needleman, Bradley ; Rutsky, Jessica ; Sun, Qinghua ; Deiuliis, Jeffrey A. ; Satoskar, Abhay R. ; Rajagopalan, Sanjay. / T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance. In: Diabetes. 2014 ; Vol. 63, No. 4. pp. 1289-1302.
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