congresos y reuniones científicas
Visceral Adipose Tissue Tregs Expressing Cd39 Are Protected From Atp Induced Cell-Death
PANDOLFI, JULIETA; FERRARO, ARIEL ; LERNER, MARTIN; PASYASLIAN, FLORENCIA; BILLORDO, ARIEL; BAZ, PLACIDA; ARRUVITO, LOURDES; FAINBOIM, LEONARDO
Mar del Plata
Congreso; LIX Reunión Científico Anual (SAIC) y LXII Reunión Anual de Sociedad Argentina de Inmunología; 2014
Sociedad Argentina de Inmunología
Background: Obesity (OB) is associated with local inflammation in visceral adipose tissue (VAT) which induces the release of ATP. Extracellular ATP as a danger signal can trigger cell- death. Its concentration is regulated by CD39 that hydrolyzes ATP/ADP into AMP. Because Regulatory T cells (Tregs) express CD39 and also CD73, which converts AMP into adenosine, they are therefore able to generate adenosine with suppressor properties. In this context we hypothesized that the expression of CD39 constitutes not only a suppressor mechanism to Tregs, but also could determine a different sensibility to ATP induced cell-death. Aims: 1-To determine functional differences between CD39+ and CD39-Tregs in VAT; 2- To analyze a differential susceptibility to ATP induced cell-death in both subsets; 3-To determine the frequency of CD39+ and CD39-Tregs in VAT of lean and obese donors. Results: Samples of VAT were obtained during endoscopic repair of hernias or bariatric surgeries from lean (LD) or obese (OB) patients, respectively. Our data demonstrate that CD39+Tregs and CD39-Tregs resident in VAT are functionally different: CD39+Tregs expressed higher levels of CD73 and secreted lower amounts of IL-10 compared to CD39-Tregs. Moreover, in the presence of ATP, CD39+Tregs showed lower levels of cell-death (Annexin+), quantified by Flow cytometry. As expected, and in accordance with the fact that extracellular ATP is increase in VAT of OB, the frequency of CD39-Tregs was lower in VAT of OB compared with LD. Conclusions: Our data suggest that CD39 expression may rescue Tregs from ATP induced cell-death. This feature could be relevant during OB associated inflammation because allows the presence of a resident Tregs population in VAT. Additionally, a decreased CD39-Tregs frequency secreting IL-10 could be important in OB as this cytokine is associated with insulin sensitivity.