It has long been believed that non-classical monocytes play a purely regulatory role in the immune system. With the help of a novel marker (PD-L1), Munich researchers at the Ludwig Maximilian University (LMU) have now shown that they are directly involved in the regulation of the immune response.
Monocytes form a functional group of white blood cells and are known to play a role in the immune system. Based on the protuberances that are on their surfaces, they can be divided into two major subtypes, called classical and non-classical monocytes, which perform different functions in the immune system. So far, non-classical monocytes have only been considered as monitoring cells that circulate in the bloodstream and serve to recruit other immune cells to sites with damage in the walls of the blood vessels. An international team around Dr. med. Johan Duchêne, Mariaelvy Bianchini, dr. Remco Megens and Professor Christian Weber from the Institute for Cardiovascular Prevention (IPEK) at the LMU Medical Center have now identified a specific marker for these cells. Using this tool, they then demonstrated in an experimental mouse model that non-classical monocytes also play a direct regulatory role in the adaptive immune response in certain tissues. The new study appears in the journal Science Immunology .
Classical monocytes migrate to sites of inflammation in the body, where they further differentiate to produce a series of specialized immune cells that activate other components of the immune response. "We were interested in whether non-classical monocytes not only act as a lookout, but also regulate other types of immune cells," says Duchêne. The problem was that no specific marker had been found for them, with which they could be reliably identified. This obstacle has now been overcome. In their studies on mice, Duchêne and his colleagues characterized a specific surface protein as a suitable marker for the tracking of non-classical monocytes. "The affected protein (PD-L1) is a known and well-studied molecule that is found on the surface of cancer cells and serves to inactivate the immune response to malignant tumor cells." It was a big surprise for us to discover this protein is also strongly expressed on the surface of non-classical monocytes, "says Bianchini, who is the first co-author involved in the study.
The new marker made it possible to show the authors of the new study That classical monocytes that develop in bone marrow are transformed into non-classical monocytes when they first come into contact with specialized blood vessels near the cortical bone. "This is the first experimental evidence that identifies both types of monocytes come from the bone marrow. For example, altered conditions in this microenvironment, caused by inflammatory reactions, can negatively impact the transformation process, "explains Megens. We have shown that this is indeed the case in the bone marrow of aging mice.
In addition, the team showed that non-classical monocytes are not adaptive immune system bit players. They can do more than serve as sentries that sound the alarm. They are able to infiltrate a specific type of inflamed tissue called tertiary lymphoid organs, for example in the context of a myocardial infarction, where they act as direct regulators of the adaptive immune response by modulating the activities of particular subgroups of other immune cells. "Our new marker has proved to be a valuable tool and will help to further elucidate the biological roles of non-classical monocytes," Weber says. "It may even allow us to discover new molecular mechanisms that contribute to the development of inflammatory diseases such as cardiovascular disease and cancer."
A class of white blood cells becomes more inflammatory with age
M. Bianchini et al., PD-L1 expression on non-classical monocytes, reveals their origin and immunoregulatory function, Science Immunology (2019). immunology.sciencemag.org/look… 6 / sciimmunol.aar3054
Researchers report on the development and immunoregulatory function of monocytes (2019, 21 June)
retrieved on June 22, 2019
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