Artículo
ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity
Pandolfi, Julieta Belen
; Ferraro, Sebastián Ariel
; Sananez, Inés
; Gancedo, Maria Clotilde; Baz, Placida
; Billordo, Luis Ariel
; Fainboim, Leonardo
; Arruvito, Maria Lourdes
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Fecha de publicación:
03/2016
Editorial:
American Association of Immunologists
Revista:
Journal of Immunology
ISSN:
0022-1767
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
ATP
,
INFLAMMATION
,
TH17
,
OBESITY
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(INIGEM)
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Pandolfi, Julieta Belen; Ferraro, Sebastián Ariel; Sananez, Inés; Gancedo, Maria Clotilde; Baz, Placida; et al.; ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity; American Association of Immunologists; Journal of Immunology; 196; 8; 3-2016; 3287-3296
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