Crosstalk between purinergic receptor P2Y and chemokine receptor CXCR7 is regulated by CXCR4 in human macrophages.

P2Y is a G protein-coupled ATP receptor that activates IL-1 receptor (IL-1R) in a cyclic AMP dependent manner. In human macrophages, P2Y/IL-1R crosstalk with CCL20 as a prime target is controlled by phosphodiesterase 4 (PDE4), which mediates breakdown of cyclic AMP. Here, we used gene expression analysis to identify activation of CXCR4 and CXCR7 as a hallmark of P2Y signaling.

P2Y/IL-1 receptor crosstalk controls macrophage inflammation: a novel target for anti-inflammatory strategies?

Although first cloning of the human ATP receptor P2Y was successful 25 years ago, the exact downstream signaling pathways of P2Y receptor, which can couple to G and G 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 P2Y expression and function. Many meaningful observations related to P2Y have been made in primary immune cells, indicating that P2Y receptors are important regulators of inflammation and cell migration, also by controlling mitochondrial activity.

The P2Y receptor of human M2 macrophages activates canonical and IL-1 receptor signaling to translate the extracellular danger signal ATP into anti-inflammatory and pro-angiogenic responses.

The cytoprotective ATP receptor P2Y is upregulated during M2 macrophage differentiation and contributes to the anti-inflammatory properties of this macrophage subset. Here, we studied P2Y-induced reprogramming of human M2 macrophages at the level of mRNA and protein expression. Upregulation of IL-1 receptor (IL-1R) and its known downstream effectors VEGF, CCL20 and SOCS3 as well as downregulation of the ATP-degrading ecto-ATPase CD39 emerged as hallmarks of P2Y activation.

Control of Macrophage Inflammation by P2Y Purinergic Receptors.

Macrophages comprise a phenotypically and functionally diverse group of hematopoietic cells. Versatile macrophage subsets engage to ensure maintenance of tissue integrity. To perform tissue stress surveillance, macrophages express many different stress-sensing receptors, including purinergic P2X and P2Y receptors that respond to extracellular nucleotides and their sugar derivatives.

The human G protein-coupled ATP receptor P2Y is a target for anti-inflammatory strategies.

Background And Purpose: The ATP receptor P2Y , which couples to G and G proteins, senses cell stress and promotes cytoprotective responses. P2Y receptors are upregulated during differentiation of M2 macrophages. However, it is unclear whether and how P2Y receptors contribute to the anti-inflammatory properties of M2 macrophages.

Peptides from allergenic lipocalins bind to formyl peptide receptor 3 in human dendritic cells to mediate T2 immunity.

Background: How T2-mediated allergic immune responses are induced is still under investigation.

Objective: In an in vitro system we compared the effect of lipocalin allergens and nonallergenic homologues on human monocyte-derived dendritic cells (DCs) to investigate how they polarize naive CD4 T cells. Microarray data gained with these DCs showed a significant difference in expression of formyl peptide receptors (FPRs).

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism.

Mucosal-associated invariant T (MAIT) cells are an abundant human T-cell subset with antimicrobial properties. They can respond to bacteria presented via antigen-presenting cells (APCs) such as macrophages, which present bacterially derived ligands from the riboflavin synthesis pathway on MR1. Moreover, MAIT cells are also highly responsive to cytokines which enhance and even substitute for T-cell receptor-mediated signaling.