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Am J Physiol Heart Circ Physiol. 2017 Mar 1;312(3):H368-H374. doi: 10.1152/ajpheart.00603.2016. Epub 2016 Dec 16.

Dendritic cells and isolevuglandins in immunity, inflammation, and hypertension.

Author information

1
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
2
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; and.
3
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; annet.kirabo@vanderbilt.edu.
4
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville Tennessee.

Abstract

Hypertension is the major risk factor for morbidity and mortality from myocardial infarction, stroke, heart failure, and chronic kidney disease. Despite its importance, the pathogenesis of essential hypertension is poorly understood. During the past several years, it has become evident that T cells contribute to hypertension. Activated T cells accumulate in the perivascular space and the kidney and release cytokines that promote vascular dysfunction and end-organ damage. Although dendritic cells play a pivotal role in initiating adaptive immune responses, T cells have taken center stage in studies implicating the immune system in the genesis of hypertension. The mechanisms by which T cells are activated and the antigens involved are poorly understood. We recently showed that hypertension is associated with increased dendritic cell production of the TH17 polarizing cytokines, IL-6, IL-1β, and IL-23. This occurs in part by increased superoxide production via NADPH oxidase and protein modification by highly reactive isolevuglandins (IsoLGs). IsoLGs are produced via the isoprostane pathway of free radical-mediated lipid peroxidation and, when adducted to proteins, have the potential to act as neoantigens. In this review, we discuss recent advances in our understanding of the role of antigen-presenting dendritic cells in the pathophysiology of hypertension and highlight potential neoantigens that may contribute to this disease.

KEYWORDS:

dendritic cells; hypertension; isolevuglandins; neoantigens

PMID:
27986660
PMCID:
PMC6146302
DOI:
10.1152/ajpheart.00603.2016
[Indexed for MEDLINE]
Free PMC Article

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