10/12/2018

Basophils - underestimated players in lung development

The adult lung consists of different, highly specialized cell types that are protected by a variety of immune cells. Using advanced single cell sequencing methods, researchers of the Weizmann Institute of Science in Israel, the Austrian Academy of Sciences and the Medical University in Vienna discovered a hitherto unknown, fundamental role of basophils in the development of macrophages in the lung. The study, published in “Cell”, could open new clinical strategies to fight lung diseases.

Zwei Lungenflügel mit astförmigen Bronchien, die sich bis in die Lungenbläschen verzweigen – so viel ist vom Aufbau der Lunge wohl den meisten bekannt. Will man das Atmungsorgan jedoch wirklich verstehen, muss man genauer hinschauen: Eine große Bandbreite spezialisierter Zellen arbeitet eng zusammen, damit die Lunge reibungslos funktioniert und der lebenswichtige Gasaustausch stattfinden kann. Darunter auch eine ganze Palette an Immunzellen, die eindringende Mikroorganismen in Schach halten und gleichzeitig dafür sorgen, dass Entzündungen beschränkt bleiben, um die Lungenfunktion nicht zu beeinträchtigen. Das erfordert ausgefeilte Kommunikation zwischen den Zelltypen und eine straff organisierte Aufgabenteilung. 

Entwicklung der Lunge beim Embryo bisher wenig erforscht

Lungs are vital organs required for the uptake of oxygen in exchange for carbon dioxide. However, the enormous complexity of the respiratory organ is often underestimated and deserves a closer look: A broad range of specialized cells work closely together to ensure the proper functioning of the lung and provide the vital gas exchange. The development and maturation of this complex organ during the embryonal stages and after birth was largely unknown. 

In the latest issue of “Cell”, scientists from Israel and Austria made an important contribution to the understanding of the pulmonary immune-development using a combination of high throughput single-cell RNA sequencing, functional assays and cutting-edge microscopy methods. The research group of Ido Amit from the Weizmann Institute of Science, together with the teams of Sylvia Knapp at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and the Department of Medicine I of the Medical University Vienna and Tibor Harkany at the Center for Brain Research of the Medical University of Vienna could establish the first comprehensive map of lung cell types and their inter-lineage crosstalk during development. 

An unexpected finding: basophils, immune cells that were hitherto held responsible for allergic reactions, reside in lungs where they develop into a special subtype that produces crucial growth factors and cytokines. These cells are different from previously described basophils that circulate in the blood, and their role in development and homeostasis, specifically in the lungs, was never reported before. Basophils broadly interact with other cell types of the lung, especially macrophages. Molecular signals, emitted by basophils, assist in the maturation of macrophages into their lung-specific phenotype, the so called alveolar macrophage. These unique signals and their impact on macrophages suggest they may play a role in lung diseases and might therefore expose and potential target for novel immunotherapies.