Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression

• Main Authors: Boudra, R. (Author), Calabrese, D.R (Author), Cleary, S.J (Author), Conrad, C. (Author), Greenland, J.R (Author), Grockowiak, E. (Author), Leavitt, A.D (Author), Looney, M.R (Author), Magnen, M. (Author), Méndez-Ferrer, S. (Author), Passegué, E. (Author), Qiu, L. (Author), Ranucci, S. (Author), Seo, Y. (Author), Swirski, F.K (Author), Valet, C. (Author), Wang, K.M (Author)
• Format: Article
• Language: English
• Published: American Society for Clinical Investigation 2022
• Online Access: View Fulltext in Publisher
• ISBN: 00219738 (ISSN)
• DOI: 10.1172/JCI153920

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. Copyright: © 2022, Valet et al.