Purinergic Receptors in Dendritic Cells

Dendritic cells (DCs) are regarded as highly effective antigen-presenting cells (APCs) and play a crucial role in immunomodulation. A growing body of research focuses on extracellular purines and their purinergic receptors in DCs. In this review, we provide an overview of the expression and function of purinergic receptors (P1 and P2) in DCs. To date, four P1 receptors (A1, A2A, A2B, A3), five P2X receptors (P2X1, P2X4, P2X5, P2X6, P2X7) and eight P2Y receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, P2Y14) have been reported to be expressed in DCs, with expression levels varying according to DC developmental stages (immature vs mature) and subsets. Functionally, P1 receptors are preferentially activated by adenosine(ADO) generated via ectonucleotidases, promoting the release of cytokines such as IL-10 and IL-23, and enhancing the activation, migration, and antigen presentation of DCs. In contrast, extracellular ATP-activated P2 receptors increase the secretion of pro-inflammatory cytokines including TNF-α, IL-1β, IL-18, and IL-12, while simultaneously inhibiting DC migration and antigen presentation efficiency. Therefore, only under the conditions that immune cells express the relevant receptors and ectonucleotidases dynamically regulate the ATP/ADO ratio can a mutually restrictive Yin-Yang relationship between P1 and P2 receptors be established, thereby safeguarding systemic immune homeostasis.