ATP DRIVES HUMAN VISCERAL ADIPOSE TISSUE T CELL BALANCE IN OBESITY

PANDOLFI, J; FERRARO, A; SANANEZ, I.; GANCEDO, M.; BAZ, P; BILLORDO, A.; ARRUVITO, L; FAINBOIM, L

Congreso; SAIC/FAIC 2015; 2015

Sociedad Argentina de Inmunología

ackground: T-cell regulation in visceral adipose tissue (VAT) provides a link between inflammation and insulin resistance. Extracellular ATP increases in inflammatory milieus playing a pivotal role in immune homeostasis. Its concentration is regulated by CD39 which is mainly expressed on Tregs. However, CD39 can also identify Th17 cells. Aims: 1) to analyze the frequency of CD39+ Teff, CD39+ Tregs and CD39- Tregs circulating in blood or residing in VAT of lean (LD) and obese donors; 2) to define CD39+ Teff phenotype in VAT of donors; 3) to identify the mechanisms by which extracellular ATP modulates CD4+ T cell balance in tissue. Results: Samples of VAT were obtained during endoscopic repair of hernias or bariatric surgeries from LD or obese patients, respectively. Our data demonstrate that CD39+ Teff were increased in obese patients VAT, while CD39- Tregs were diminished in this tissue. Moreover this group expressed increased levels of Th17 markers (RORC, CD39, IL-23 receptor and IL-17) compared to LD. Additionally, we show that ATP acting via the P2X7 receptor pathway not only promoted a Th17 polarizing microenvironment (high levels of IL-1beta, IL-6 and IL-23 cytokines) but also induced cell- death in resident CD39-Tregs. Conclusions: We demonstrate that signaling through purinergic receptors drives adaptive Th17 but impairs Treg immune response in human VAT, which have implications in the pathogenesis of obesity.