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News | 18/07/2024 | Medicine, Medical research

Immune cells monitor the maturation of platelets in the bone marrow

In collaboration with international colleagues, an LMU team has discovered how certain immune cells control the formation of new megakaryocytes from progenitor cells in the bone marrow.
Platelets play an essential role in wound healing. Underproduction can lead to devastating bleeding, while overproduction increases the fatal risk of thrombosis. Maintaining a constant platelet level in the blood (homeostasis) is therefore of crucial importance. Platelets are continuously produced by megakaryocytes (MK) and released into the blood. Researchers at the LMU University Hospital and the Biomedical Center Munich (BMC ) have now made a groundbreaking discovery: cells of the innate immune system, so-called plasmacytoid dendritic cells (pDCs), are largely responsible for controlling the maturation of new MKs and thus the formation of platelets. In addition, the pDCs adapt the quantity of MKs precisely to the body's needs. The researchers have published their findings in the journal Nature. To find out how platelets develop (megakaryopoiesis), the lead authors - Florian Gärtner, Hellen Ishikawa-Ankerhold, Susanne Stutte and Wenwen Fu - investigated the place where platelets are formed: the bone marrow.
LMU Klinikum
Tissue homeostasis: plasmacytoid dendritic cells monitor the bone marrow and initiate the formation of megakaryocytes as required Even distribution of megakaryocytes (green) controlled by plasmacytoid dendritic cells (magenta) in a human bone marrow slice.

Cells of the innate immune system control megakaryopoiesis

They discovered that the progenitor cells of megakaryopoiesis are completely consumed and constantly replaced during platelet formation (thrombopoiesis). This crucial process is controlled by the cells of the innate immune system, the pDCs. It was already known that pDCs patrol the blood in small amounts to be one of the first immune cells to rapidly initiate viral defense.

"We have identified a new process in which pDCs also patrol the bone marrow and continuously 'measure' the stock of depleted megakaryocytes," say the first authors. By releasing messenger substances, the pDCs stimulate megakaryopoiesis from progenitor cells as required. And the immune system controls the homeostasis of the megakaryocytes on this basis.


Possible approaches for therapies

Since pDCs also play a role in the defense against viral pathogens and can be activated accordingly by viral infections, we find a previously unknown connection between infections such as Covid-19 and influenza and their effects on platelet formation. "In patients with severe Covid-19, we found an accumulation of activated pDCs in the bone marrow tissue," says Gärtner. "The pDCs were in close contact with MKs, which also correlated with an excessive amount of MK in these patients."

The researchers hypothesize that pharmacological modulation of the pDC-mediated homeostatic circuit could benefit these patients. The discovery of this mechanism could form the basis for research into new treatments for Covid-19 and other diseases associated with impaired platelet production. "Targeted modulation of pDC-driven megakaryopoiesis offers opportunities to increase or suppress platelet production in different clinical scenarios," explains Gärtner.

Originally translated with DeepL