Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity
A successful immune response must effectively obtain pathogen clearance upon infection while preventing excessive collateral tissue damage. It is therefore essential to achieve a nuanced fine regulation of pro- and anti-inflammatory signals to orchestrate the optimal immune function and restore home...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825003093 |
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| Summary: | A successful immune response must effectively obtain pathogen clearance upon infection while preventing excessive collateral tissue damage. It is therefore essential to achieve a nuanced fine regulation of pro- and anti-inflammatory signals to orchestrate the optimal immune function and restore homeostatic conditions. In this process, the purinergic system plays the dual role of promoting host antimicrobial effector mechanisms while simultaneously limiting the immune response to the site and duration of infection. This double-edged nature of the purinergic system can also be observed in the modulation of autoimmune conditions. This review aims to provide a thorough overview of P2Y receptor downstream signalling and, for the first time, to illustrate the current state of knowledge on the incompletely understood crosstalk of P2Y receptors with Toll-like receptor (TLR) and inflammasome activation respectively. Additionally, it evaluates the therapeutic potential of targeting P2Y receptors in the context of inflammatory diseases. Recent pre-clinical and clinical studies of P2Y receptors are being presented and put into perspective by highlighting the importance of biased signalling and novel pharmacological strategies. |
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| ISSN: | 1096-1186 |