The role of infiltrating immune cells in dysfunctional adipose tissue

Guzik, T. J., Skiba, D. S., Touyz, R. M. and Harrison, D. G. (2017) The role of infiltrating immune cells in dysfunctional adipose tissue. Cardiovascular Research, 113(9), pp. 1009-1023. (doi:10.1093/cvr/cvx108) (PMID:28838042)

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Abstract

Adipose tissue (AT) dysfunction, characterized by loss of its homeostatic functions, is a hallmark of non-communicable diseases. It is characterized by chronic low-grade inflammation and is observed in obesity, metabolic disorders such as insulin resistance and diabetes. While classically it has been identified by increased cytokine or chemokine expression, such as increased MCP-1, RANTES, IL-6, interferon (IFN) gamma or TNFα, mechanistically, immune cell infiltration is a prominent feature of the dysfunctional AT. These immune cells include M1 and M2 macrophages, effector and memory T cells, IL-10 producing FoxP3+ T regulatory cells, natural killer and NKT cells and granulocytes. Immune composition varies, depending on the stage and the type of pathology. Infiltrating immune cells not only produce cytokines but also metalloproteinases, reactive oxygen species, and chemokines that participate in tissue remodelling, cell signalling, and regulation of immunity. The presence of inflammatory cells in AT affects adjacent tissues and organs. In blood vessels, perivascular AT inflammation leads to vascular remodelling, superoxide production, endothelial dysfunction with loss of nitric oxide (NO) bioavailability, contributing to vascular disease, atherosclerosis, and plaque instability. Dysfunctional AT also releases adipokines such as leptin, resistin, and visfatin that promote metabolic dysfunction, alter systemic homeostasis, sympathetic outflow, glucose handling, and insulin sensitivity. Anti-inflammatory and protective adiponectin is reduced. AT may also serve as an important reservoir and possible site of activation in autoimmune-mediated and inflammatory diseases. Thus, reciprocal regulation between immune cell infiltration and AT dysfunction is a promising future therapeutic target.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harrison, Professor David and Guzik, Professor Tomasz and Skiba, Mr Dominik and Touyz, Professor Rhian
Authors: Guzik, T. J., Skiba, D. S., Touyz, R. M., and Harrison, D. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Cardiovascular Research
Publisher:Oxford University Press
ISSN:0008-6363
ISSN (Online):1755-3245
Published Online:11 July 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Cardiovascular Research 113(9):1009-1023
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES

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