A team of Swedish researchers has revealed how different kinds of immune cells, called macrophages, develop in the lungs, and which of them may be behind severe lung diseases, a discovery that may contribute to future treatments for Covid-19, among other diseases.To date, research on the development of human lung macrophages has been limited.In a new study published in Immunity, researchers at Karolinska Institutet in Sweden used a model to study the development of lung macrophages directly in a living lung.This has been combined with a method to study gene activity in individual cells, RNA sequencing, and thereby discovered how blood monocytes become human lung macrophages."In our study, we show that classical monocytes migrate into airways and lung tissue and are converted into macrophages that protect the health and function of the lungs," said Tim Willinger, Associate Professor at the Department of Medicine who led the study."We have also identified a special kind of monocyte, HLA-DRhi, which is an intermediate immune cell between a blood monocyte and an airway macrophage."These HLA-DRhi monocytes can leave the blood circulation and migrate into the lung tissue.Macrophages are immune cells that, among other things, protect the lungs from such attacks.But under certain conditions, lung macrophages can also contribute to severe lung diseases, such as chronic obstructive pulmonary disease (COPD) and Covid-19.The non-classical monocytes, however, develop into macrophages in the many blood vessels of the lungs and do not migrate into the lung tissue.In an infection with the novel coronavirus, SARS-COV-2, which causes Covid-19, researchers believe that protective, anti-inflammatory macrophages are replaced by pro-inflammatory lung macrophages from blood monocytes."Given their important role in rapid inflammatory responses, our results indicate that future treatments should focus on inflammatory macrophages and monocytes to reduce lung damage and mortality from severe Covid-19," said Willinger.