Cargando…

Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection

Platelets play a role not only in hemostasis and thrombosis, but also in inflammation and innate immunity. We previously reported that an activated form of tyrosyl-tRNA synthetase (YRS(ACT)) has an extratranslational activity that enhances megakaryopoiesis and platelet production in mice. Here, we r...

Descripción completa

Detalles Bibliográficos
Autores principales: Morodomi, Yosuke, Kanaji, Sachiko, Sullivan, Brian M., Zarpellon, Alessandro, Orje, Jennifer N., Won, Eric, Shapiro, Ryan, Yang, Xiang-Lei, Ruf, Wolfram, Schimmel, Paul, Ruggeri, Zaverio M., Kanaji, Taisuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860251/
https://www.ncbi.nlm.nih.gov/pubmed/36409883
http://dx.doi.org/10.1073/pnas.2212659119
_version_ 1784874539041161216
author Morodomi, Yosuke
Kanaji, Sachiko
Sullivan, Brian M.
Zarpellon, Alessandro
Orje, Jennifer N.
Won, Eric
Shapiro, Ryan
Yang, Xiang-Lei
Ruf, Wolfram
Schimmel, Paul
Ruggeri, Zaverio M.
Kanaji, Taisuke
author_facet Morodomi, Yosuke
Kanaji, Sachiko
Sullivan, Brian M.
Zarpellon, Alessandro
Orje, Jennifer N.
Won, Eric
Shapiro, Ryan
Yang, Xiang-Lei
Ruf, Wolfram
Schimmel, Paul
Ruggeri, Zaverio M.
Kanaji, Taisuke
author_sort Morodomi, Yosuke
collection PubMed
description Platelets play a role not only in hemostasis and thrombosis, but also in inflammation and innate immunity. We previously reported that an activated form of tyrosyl-tRNA synthetase (YRS(ACT)) has an extratranslational activity that enhances megakaryopoiesis and platelet production in mice. Here, we report that YRS(ACT) mimics inflammatory stress inducing a unique megakaryocyte (MK) population with stem cell (Sca1) and myeloid (F4/80) markers through a mechanism dependent on Toll-like receptor (TLR) activation and type I interferon (IFN-I) signaling. This mimicry of inflammatory stress by YRS(ACT) was studied in mice infected by lymphocytic choriomeningitis virus (LCMV). Using Sca1/EGFP transgenic mice, we demonstrated that IFN-I induced by YRS(ACT) or LCMV infection suppressed normal hematopoiesis while activating an alternative pathway of thrombopoiesis. Platelets of inflammatory origin (Sca1/EGFP(+)) were a relevant proportion of those circulating during recovery from thrombocytopenia. Analysis of these “inflammatory” MKs and platelets suggested their origin in myeloid/MK-biased hematopoietic stem cells (HSCs) that bypassed the classical MK-erythroid progenitor (MEP) pathway to replenish platelets and promote recovery from thrombocytopenia. Notably, inflammatory platelets displayed enhanced agonist-induced activation and procoagulant activities. Moreover, myeloid/MK-biased progenitors and MKs were mobilized from the bone marrow, as evidenced by their presence in the lung microvasculature within fibrin-containing microthrombi. Our results define the function of YRS(ACT) in platelet generation and contribute to elucidate platelet alterations in number and function during viral infection.
format Online
Article
Text
id pubmed-9860251
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher National Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-98602512023-02-01 Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection Morodomi, Yosuke Kanaji, Sachiko Sullivan, Brian M. Zarpellon, Alessandro Orje, Jennifer N. Won, Eric Shapiro, Ryan Yang, Xiang-Lei Ruf, Wolfram Schimmel, Paul Ruggeri, Zaverio M. Kanaji, Taisuke Proc Natl Acad Sci U S A Biological Sciences Platelets play a role not only in hemostasis and thrombosis, but also in inflammation and innate immunity. We previously reported that an activated form of tyrosyl-tRNA synthetase (YRS(ACT)) has an extratranslational activity that enhances megakaryopoiesis and platelet production in mice. Here, we report that YRS(ACT) mimics inflammatory stress inducing a unique megakaryocyte (MK) population with stem cell (Sca1) and myeloid (F4/80) markers through a mechanism dependent on Toll-like receptor (TLR) activation and type I interferon (IFN-I) signaling. This mimicry of inflammatory stress by YRS(ACT) was studied in mice infected by lymphocytic choriomeningitis virus (LCMV). Using Sca1/EGFP transgenic mice, we demonstrated that IFN-I induced by YRS(ACT) or LCMV infection suppressed normal hematopoiesis while activating an alternative pathway of thrombopoiesis. Platelets of inflammatory origin (Sca1/EGFP(+)) were a relevant proportion of those circulating during recovery from thrombocytopenia. Analysis of these “inflammatory” MKs and platelets suggested their origin in myeloid/MK-biased hematopoietic stem cells (HSCs) that bypassed the classical MK-erythroid progenitor (MEP) pathway to replenish platelets and promote recovery from thrombocytopenia. Notably, inflammatory platelets displayed enhanced agonist-induced activation and procoagulant activities. Moreover, myeloid/MK-biased progenitors and MKs were mobilized from the bone marrow, as evidenced by their presence in the lung microvasculature within fibrin-containing microthrombi. Our results define the function of YRS(ACT) in platelet generation and contribute to elucidate platelet alterations in number and function during viral infection. National Academy of Sciences 2022-11-21 2022-11-29 /pmc/articles/PMC9860251/ /pubmed/36409883 http://dx.doi.org/10.1073/pnas.2212659119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Morodomi, Yosuke
Kanaji, Sachiko
Sullivan, Brian M.
Zarpellon, Alessandro
Orje, Jennifer N.
Won, Eric
Shapiro, Ryan
Yang, Xiang-Lei
Ruf, Wolfram
Schimmel, Paul
Ruggeri, Zaverio M.
Kanaji, Taisuke
Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection
title Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection
title_full Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection
title_fullStr Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection
title_full_unstemmed Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection
title_short Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection
title_sort inflammatory platelet production stimulated by tyrosyl-trna synthetase mimicking viral infection
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860251/
https://www.ncbi.nlm.nih.gov/pubmed/36409883
http://dx.doi.org/10.1073/pnas.2212659119
work_keys_str_mv AT morodomiyosuke inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT kanajisachiko inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT sullivanbrianm inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT zarpellonalessandro inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT orjejennifern inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT woneric inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT shapiroryan inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT yangxianglei inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT rufwolfram inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT schimmelpaul inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT ruggerizaveriom inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection
AT kanajitaisuke inflammatoryplateletproductionstimulatedbytyrosyltrnasynthetasemimickingviralinfection