Immune cells monitor platelet maturation in the bone marrow

Platelets (thrombocytes) are vital players in wound healing. Too few platelets can cause devastating haemorrhages, while an overproduction increases the fatal risk of thrombosis. Keeping the number of platelets in the blood constant (homeostasis) is therefore of central importance. Platelets are continuously produced by megakaryocytes (MKs) and released into the blood. Researchers at the LMU Hospital and the Biomedical Centre (BMC) have now made a groundbreaking discovery: cells of the innate immune system (plasmacytoid dendritic cells; pDCs) play a key role in controlling the maturation of new MKs and thus also the formation of platelets. In addition, pDCs precisely adapt the quantity of MKs to the body's requirements. The researchers published their findings in the journal Nature.

In order to find out how MKs are formed (megakaryopoiesis), the first authors, consisting of DZHK scientist Florian Gärtner, Hellen Ishikawa-Ankerhold, Susanne Stutte and Wenwen Fu, took a look at the place where MKs are formed, the bone marrow.

Cells of the innate immune system control megakaryopoiesis
 

They found that the precursor cells of MKs are completely consumed and constantly replaced during platelet formation (thrombopoiesis). This crucial process is regulated by cells of the innate immune system, the pDCs. pDCs were previously known to patrol the blood in small quantities in order to be one of the first immune cells to initiate a viral defence.

"Here we have identified a new process in which pDCs also patrol within the bone marrow and "measure" how large the population of consuming megakaryocytes is at any time," say the first authors. By releasing their messenger substances, pDCs stimulate megakaryopoiesis from progenitor cells when required. The immune system therefore controls the homeostasis of MKs."

Possible approach for therapies

As pDCs also play a role in the defence against viral pathogens and are activated accordingly during viral infections, this is where the previously unknown link between infections such as COVID-19 and influenza and their effects on platelet formation can be found. "In patients with severe COVID-19 disease, we were able to detect 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 MK count in these patients."

The researchers suspect that pharmacological modulation of the pDC-mediated homeostatic cycle may be beneficial for these patients. Uncovering this mechanism could form the basis for research into new treatment methods for COVID-19 and other diseases associated with deregulated platelet production. "Targeting pDC-driven megakaryopoiesis offers opportunities to increase or suppress platelet production in various clinical scenarios," explains Gärtner.

Original publication: Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis (Gaertner et al., 2024)

The paper was named Paper of the Month July 2024.

Source: press release LMU (in German only)