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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| Language: | English |
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Elsevier
2025-09-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825003093 |
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| author | Lena Rueschpler Sebastian Schloer |
| author_facet | Lena Rueschpler Sebastian Schloer |
| author_sort | Lena Rueschpler |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-287bcb2583fe4ec2ae4f5ba58e00fa78 |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-287bcb2583fe4ec2ae4f5ba58e00fa782025-08-20T03:58:17ZengElsevierPharmacological Research1096-11862025-09-0121910788410.1016/j.phrs.2025.107884Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunityLena Rueschpler0Sebastian Schloer1Institute for Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, GermanyInstitute for Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, Germany; Corresponding author at: Institute for Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.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.http://www.sciencedirect.com/science/article/pii/S1043661825003093P2Y receptorsToll-like receptorsAutoimmunityInfectionTherapeutic strategies |
| spellingShingle | Lena Rueschpler Sebastian Schloer Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity Pharmacological Research P2Y receptors Toll-like receptors Autoimmunity Infection Therapeutic strategies |
| title | Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity |
| title_full | Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity |
| title_fullStr | Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity |
| title_full_unstemmed | Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity |
| title_short | Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity |
| title_sort | beyond the surface p2y receptor downstream pathways tlr crosstalk and therapeutic implications for infection and autoimmunity |
| topic | P2Y receptors Toll-like receptors Autoimmunity Infection Therapeutic strategies |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825003093 |
| work_keys_str_mv | AT lenarueschpler beyondthesurfacep2yreceptordownstreampathwaystlrcrosstalkandtherapeuticimplicationsforinfectionandautoimmunity AT sebastianschloer beyondthesurfacep2yreceptordownstreampathwaystlrcrosstalkandtherapeuticimplicationsforinfectionandautoimmunity |