Journal article
CD40-mediated maintenance of immune homeostasis in the adipose tissue microenvironment
Diabetes (New York, N.Y.), Vol.63(8), pp.2751-2760
08/2014
DOI: 10.2337/db13-1657
PMCID: PMC4392912
PMID: 24647739
Abstract
Chronic inflammation in visceral adipose tissue is considered a key element for induction of insulin resistance in obesity. CD40 is required for efficient systemic adaptive immune responses and is implicated in various inflammatory conditions. However, its role in modulating immunity in the microanatomical niches of adipose tissue remains largely undefined. Here, we show that, in contrast to its well-documented costimulatory effects, CD40 regulates development of insulin resistance in a diet-induced obesity (DIO) mouse model by ameliorating local inflammation in adipose tissues. CD40 deficiency (CD40KO) resulted in greater body weight gain, more severe inflammation in epididymal adipose tissue (EAT), and aggravated insulin resistance in response to DIO. Interestingly, we found that CD40KO CD8(+) T lymphocytes were major contributors to exacerbated insulin resistance. Specifically, CD8(+) T cells in EAT of DIO CD40KO mice produced elevated chemokines and proinflammatory cytokines and were critical for macrophage recruitment. These results indicate that CD40 plays distinct roles in different tissues and, unexpectedly, plays an important role in maintaining immune homeostasis in EAT. Further study of how CD40 promotes maintenance of healthy metabolism could contribute to better understanding of and ability to therapeutically manipulate the increasing health problem of obesity and insulin resistance.
Details
- Title: Subtitle
- CD40-mediated maintenance of immune homeostasis in the adipose tissue microenvironment
- Creators
- Zuoan Yi - Department of Microbiology, University of Iowa, Iowa City, IALaura L Stunz - Department of Microbiology, University of Iowa, Iowa City, IAGail A Bishop - Department of Microbiology, University of Iowa, Iowa City, IADepartment of Internal Medicine, University of Iowa, Iowa City, IAGraduate Immunology Program, University of Iowa, Iowa City, IAVA Medical Center, Iowa City, IA gail-bishop@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.63(8), pp.2751-2760
- Publisher
- United States
- DOI
- 10.2337/db13-1657
- PMID
- 24647739
- PMCID
- PMC4392912
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- I01 BX001702 / BLRD VA P30 ES005605 / NIEHS NIH HHS
- Language
- English
- Date published
- 08/2014
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984002399402771
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