The Journal of Clinical Investigation (Apr 2022)

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

  • Colin Valet,
  • Mélia Magnen,
  • Longhui Qiu,
  • Simon J. Cleary,
  • Kristin M. Wang,
  • Serena Ranucci,
  • Elodie Grockowiak,
  • Rafik Boudra,
  • Catharina Conrad,
  • Yurim Seo,
  • Daniel R. Calabrese,
  • John R. Greenland,
  • Andrew D. Leavitt,
  • Emmanuelle Passegué,
  • Simón Méndez-Ferrer,
  • Filip K. Swirski,
  • Mark R. Looney

Journal volume & issue
Vol. 132, no. 7

Abstract

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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.

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