Basophils role in lung development

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. Among those cells are various immune cells, which keep invading microorganisms in check while at the same time preventing harmful inflammation.

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 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 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.

Authors show that basophils establish a lung-specific function imprinted by IL-33 and granulocyte-macrophage colony-stimulating factor (GM-CSF), characterized by unique signaling of cytokines and growth factors important for stromal, epithelial, and myeloid cell fates.

"We were able to show that the development of the lung proceeds in several waves, and that lung resident basophils are important players," co-first author of the study, explains.

Antibody-depletion strategies, diphtheria toxin-mediated selective depletion of basophils, and co-culture studies show that lung resident basophils are important regulators of alveolar macrophage development and function. "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."

Antibody-depletion strategies, diphtheria toxin-mediated selective depletion of basophils, and co-culture studies show that lung resident basophils are important regulators of alveolar macrophage development and function.

"This discovery is very interesting, even from a medical point of view," Principal Investigator adds. "The unique signals of basophils and their impact on macrophages suggest they may play a role in lung diseases and might therefore expose and potential target for novel immunotherapies."