Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression.
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Authors
Valet, Colin
Magnen, Mélia
Qiu, Longhui
Cleary, Simon J
Wang, Kristin M
Ranucci, Serena
Grockowiak, Elodie
Boudra, Rafik
Conrad, Catharina
Seo, Yurim
Calabrese, Daniel R
Greenland, John R
Leavitt, Andrew D
Passegué, Emmanuelle
Méndez-Ferrer, Simón
Swirski, Filip K
Looney, Mark R
Publication Date
2022-04-01Journal Title
J Clin Invest
ISSN
0021-9738
Publisher
American Society for Clinical Investigation
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Valet, C., Magnen, M., Qiu, L., Cleary, S. J., Wang, K. M., Ranucci, S., Grockowiak, E., et al. (2022). Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression.. J Clin Invest https://doi.org/10.1172/JCI153920
Abstract
Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet production and phenotypes of resultant platelets. Here, we showed during sepsis that the spleen was a major site of megakaryopoiesis and platelet production. Sepsis provoked an adrenergic-dependent mobilization of megakaryocyte-erythrocyte progenitors (MEPs) from the bone marrow to the spleen, where IL-3 induced their differentiation into megakaryocytes (MKs). In the spleen, immune-skewed MKs produced a CD40 ligandhi platelet population with potent immunomodulatory functions. Transfusions of post-sepsis platelets enriched from splenic production enhanced immune responses and reduced overall mortality in sepsis-challenged animals. These findings identify a spleen-derived protective platelet population that may be broadly immunomodulatory in acute inflammatory states such as sepsis.
Sponsorship
NHS Blood and Transplant
European Union's Horizon 2020 (ERC-2014-CoG-648765)
MRC-AMED (MR/V005421/1)
Funder references
European Research Council (648765)
NHS Blood and Transplant (NHSBT)
Cancer Research UK (C61367/A26670)
MRC (MR/V005421/1)
Identifiers
External DOI: https://doi.org/10.1172/JCI153920
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334392
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