P2X4 receptor as a modulator in the function of P2X receptor in CD4+ T cells from peripheral blood and adipose tissue

Abstract

Obesity is characterized by immune cell infiltration and inflammation. Purinergic receptors such as P2X1, 4 and 7 are expressed on immune cells and their activation contributes with an inflammatory response. However, the simultaneous expression of P2X1, 4 and 7 during overweight or obesity have not been described. Therefore, the aim of this study was to determine single and simultaneously expression and function of the P2X1, 4 and 7 receptors in lymphocytes and CD4 + T cells from peripheral blood (PB) and adipose tissue (AT). Our results showed a higher expression of the P2X4 receptor on CD4 + T cells from PB regarding P2X7 and P2X1 receptor expression. In addition, P2X4 receptor expression on CD4 + T cells from PB and AT was increased in individuals with BMI ≥ 25 Kg/m2. Moreover, a higher simultaneous expression of the P2X4 and P2X7 receptors on CD4 + T cells from AT compared to CD4 + T cells expressing P2X1 and P2X7 receptors simultaneously. Besides, CD4 + T cells expressing P2X4 and P2X7 receptors from PB and AT were augmented in individuals with BMI ≥ 25 Kg/m2. In addition, the percentage of lymphocytes and also CD4 + T cells expressing P2X4 receptor were elevated both in PB and AT compared to cells expressing P2X7 or P2X1. However, CD4 + T cells expressing P2X4 and P2X7 were augmented in AT compared to PB. The function of the receptors showed a lower shedding of CD62 L in adipose tissue mononuclear cells (ATMC) compared with peripheral blood mononuclear cells (PBMC) and a greater participation of P2X4 in the mobilization of intracellular calcium. We concluded that it was possible to determine for the first time the simultaneous expression of purinergic receptors in ATMC, where the P2X4 receptor has a greater participation in the activation of CD4 + T cells possibly modulating the function of the other two receptors.