IL-1R8, also known as single Ig IL-1-Related Receptor (SIGIRR) or TIR8, is a member of the IL-1R family that negatively regulates responses to IL-1R family members and TLRs. Here we report that IL-1R8 is expressed on human and murine platelets and megakaryocytes. Despite normal levels of circulating platelets IL1R8-deficient (Il1r8-/-) mice showed increased homotypic and heterotypic (platelet-neutrophil) aggregation triggered by ADP and IL-1 or LPS. Moreover IL-1R8-deficient mice showed increased soluble P-selectin levels and increased platelet-neutrophil aggregates after systemic LPS administration. Commensal flora depletion and IL-1R1 deficiency abated platelet hyperactivity and the increased platelet/neutrophil aggregation observed in Il1r8-/- mice in vitro and in vivo, suggesting a key role of IL-1R8 in regulating platelet TLR and IL-1R1 function. In a mouse model of platelet-dependent pulmonary thromboembolism, IL-1R8-deficient mice showed an increased frequency of blood vessel complete obstruction. Finally, in a small cohort of patients with severe systemic inflammatory conditions, the expression of platelet IL-1R8 was dramatically abated and it was associated to platelet-derived microparticle release. Altogether our results highlight a new and efficient mechanism through which platelets, which have a large repertoire of TLRs and IL-1 receptors, regulate thrombocyte activity and identifie IL-1R8 as a novel non-redundant player in tuning platelet activation during immunity and inflammation.

Expression and functions of IL-1R8 (TIR8/SIGIRR), a regullatory member of the IL-1 receptor family in platelets / A. Anselmo, F. Riva, S. Gentile, C. Soldani, M. Barbagallo, C. Mazzon, F. Feruglio, N. Polentarutti, P. Carullo, C. Angelini, M. Bacci, G.L. Mendolicchio, A. Voza, M. Nebuloni, A. Mantovani, C. Garlanda - In: Immunotherapy: harnessing the power of the immune system[s.l] : Flipping book publisher, 2016 Aug. - pp. 282-282 (( Intervento presentato al 15. convegno International Congress of Immunology tenutosi a Melbourne nel 2016.

Expression and functions of IL-1R8 (TIR8/SIGIRR), a regullatory member of the IL-1 receptor family in platelets

A. Anselmo
Primo
;
F. Riva
Secondo
;
S. Gentile;G.L. Mendolicchio;M. Nebuloni;
2016

Abstract

IL-1R8, also known as single Ig IL-1-Related Receptor (SIGIRR) or TIR8, is a member of the IL-1R family that negatively regulates responses to IL-1R family members and TLRs. Here we report that IL-1R8 is expressed on human and murine platelets and megakaryocytes. Despite normal levels of circulating platelets IL1R8-deficient (Il1r8-/-) mice showed increased homotypic and heterotypic (platelet-neutrophil) aggregation triggered by ADP and IL-1 or LPS. Moreover IL-1R8-deficient mice showed increased soluble P-selectin levels and increased platelet-neutrophil aggregates after systemic LPS administration. Commensal flora depletion and IL-1R1 deficiency abated platelet hyperactivity and the increased platelet/neutrophil aggregation observed in Il1r8-/- mice in vitro and in vivo, suggesting a key role of IL-1R8 in regulating platelet TLR and IL-1R1 function. In a mouse model of platelet-dependent pulmonary thromboembolism, IL-1R8-deficient mice showed an increased frequency of blood vessel complete obstruction. Finally, in a small cohort of patients with severe systemic inflammatory conditions, the expression of platelet IL-1R8 was dramatically abated and it was associated to platelet-derived microparticle release. Altogether our results highlight a new and efficient mechanism through which platelets, which have a large repertoire of TLRs and IL-1 receptors, regulate thrombocyte activity and identifie IL-1R8 as a novel non-redundant player in tuning platelet activation during immunity and inflammation.
Settore VET/05 - Malattie Infettive degli Animali Domestici
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/452447
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