Th2‐dependent disappearance and phenotypic conversion of mouse alveolar macrophages

• Published in: European journal of immunology 2023-10, Vol.53 (10), p.e2350475-n/a
• Main Authors: Dietschmann, Axel, Ruhl, Andreas, Murray, Peter J., Günther, Claudia, Becker, Christoph, Fallon, Padraic, Voehringer, David
• Format: Article
• Language: English
• Subjects: Allergic asthma; Alternatively activated macrophages; Alveolar macrophages; Alveoli; Aspergillus; Asthma; Giant cells; Helper cells; Homeostasis; Inflammation; Lungs; Lymphocytes T; Macrophages; Monocytes; Multinucleated giant cells; Progenitor cells; Respiratory function; STAT6; Stat6 protein
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202350475

Alveolar macrophages (alvMs) play an important role for maintenance of lung function by constant removal of cellular debris in the alveolar space. They further contribute to defense against microbial or viral infections and limit tissue damage during acute lung injury. alvMs arise from embryonic progenitor cells, seed the alveoli before birth, and have life‐long self‐renewing capacity. However, recruited monocytes may also help to restore the alvM population after depletion caused by toxins or influenza virus infection. At present, the population dynamics and cellular plasticity of alvMs during allergic lung inflammation is poorly defined. To address this point, we used a mouse model of Aspergillus fumigatus‐induced allergic lung inflammation and observed that Th2‐derived IL‐4 and IL‐13 caused almost complete disappearance of alvMs. This effect required STAT6 expression in alvMs and also occurred in various other settings of type 2 immunity‐mediated lung inflammation or administration of IL‐4 complexes to the lung. In addition, Th2 cells promoted conversion of alvMs to alternatively activated macrophages and multinucleated giant cells. Given the well‐established role of alvMs for maintenance of lung function, this process may have implications for resolution of inflammation and tissue homeostasis in allergic asthma. T‐cell‐derived IL‐4/IL‐13 acts directly on Siglec‐F+CD11c+ alveolar macrophages (alvM) to induce their disappearance. Cell death is probably not the main reason for this effect. Rather, alvM either phenotypically convert to Siglec‐FloCD11clo but PD‐L2+CD11b+ expressing alternatively activated macrophages (AAM) or they retain expressed of Siglec‐F and CD11c and form multinucleated giant cells (MGCs).