ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity

Obesity-induced inflammation is conducted by a metabolic pathway, which eventually causes activation of specialized immune cells and leads to an unresolved inflammatory response within the tissue. For this reason, it is critically important to determine how hypertrophic fat tissue alters T cell bala...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2016-04, Vol.196 (8), p.3287-3296
Main Authors: Pandolfi, Julieta B, Ferraro, Ariel A, Sananez, Inés, Gancedo, Maria C, Baz, Plácida, Billordo, Luis A, Fainboim, Leonardo, Arruvito, Lourdes
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adult
Antigens, CD - biosynthesis
Apoptosis - physiology
Apyrase - biosynthesis
Cellular Microenvironment - immunology
Female
Humans
Inflammation - immunology
Interleukin-17 - metabolism
Interleukin-1beta - metabolism
Interleukin-6 - metabolism
Intra-Abdominal Fat - cytology
Intra-Abdominal Fat - immunology
Intra-Abdominal Fat - pathology
Male
Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism
Obesity - immunology
Obesity - pathology
Receptors, Interleukin - metabolism
Receptors, Purinergic P2X7 - metabolism
Th17 Cells - immunology
Th17 Cells - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Obesity-induced inflammation is conducted by a metabolic pathway, which eventually causes activation of specialized immune cells and leads to an unresolved inflammatory response within the tissue. For this reason, it is critically important to determine how hypertrophic fat tissue alters T cell balance to drive inflammation. In this study, we identify the purinergic signaling as a novel mechanism driving the adaptive Th17 response in human visceral adipose tissue (VAT) of metabolically unhealthy obese patients. We demonstrate that ATP acting via the P2X7 receptor pathway promotes a Th17 polarizing microenvironment with high levels of IL-1β, IL-6, and IL-17 in VAT explants from lean donors. Moreover, in vitro blockade of the P2X7 receptor abrogates the levels of these cytokines. These findings are consistent with a greater frequency of Th17 cells in tissue from metabolically unhealthy obese donors, revealed not only by the presence of a baseline Th17-promoting milieu, but also by the higher expression of steadily recognized Th17 markers, such as RORC, IL-17 cytokine, and IL-23R, in comparison with metabolically healthy obese and lean donors. In addition, we demonstrate that CD39 expression on CD4(+)effector T cells represents a novel Th17 marker in the inflamed VAT, which also confers protection against ATP-induced cell death. The manipulation of the purinergic signaling might represent a new therapeutic target to shift the CD4(+)T cell balance under inflammatory conditions.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1502506