P2Y11/IL-1 receptor crosstalk controls macrophage inflammation: a novel target for anti-inflammatory strategies?

Abstract

Although first cloning of the human ATP receptor P2Y11 was successful 25 years ago, the exact downstream signaling pathways of P2Y11 receptor, which can couple to Gq and Gs proteins, have remained unclear. Especially the lack of rodent models as well as the limited availability of antibodies and pharmacological tools have hampered examination of P2Y11 expression and function. Many meaningful observations related to P2Y11 have been made in primary immune cells, indicating that P2Y11 receptors are important regulators of inflammation and cell migration, also by controlling mitochondrial activity. Our recent studies have shown that P2Y11 is upregulated during macrophage development and activates signaling through IL-1 receptor, which is well known for its ability to direct inflammatory and migratory processes. This review summarizes the results of the first transcriptomic and secretomic analyses of both, ectopic and native P2Y11 receptors, and discusses how P2Y11 crosstalk with the IL-1 receptor may govern anti-inflammatory and pro-angiogenic processes in human M2 macrophages.

Crosstalk between purinergic receptor P2Y11 and chemokine receptor CXCR7 is regulated by CXCR4 in human macrophages

“…It is the only member of the P2Y family that couples to G q and G s proteins (Fig. 9 ) [ 24 ]. P2Y 11 ’s other peculiarity is that it cannot be detected in rodents.…”

“…P2Y 11 is a class A GPCR that translates the danger signal ATP into adaptive responses [ 23 , 24 ]. Among its striking features are the dual coupling to G q and G s proteins as well as its absence in rodents [ 25 ], what made corresponding animal models impossible.…”

Cell Heterogeneity and Variability in Peripheral Nerve after Injury

“…TNF and IL-6 from activated SCs not only activate local macrophages but also recruit monocytes to the injured site [ 64 ]. In turn, macrophages secrete pro-inflammatory factors like IL-1 which stimulate SCs to synthesize and secrete neurotrophic factors to guide axon regeneration [ 65 ]. When it comes to 9 d post-injury, the collagen–integrin, EPHRIN–EPH, and FGF–FGFR interactions between subtypes of fibroblasts were the most significant, which may respond to the recombination of the extracellular matrix during axon regeneration [ 66 ].…”