IL11 negatively impacts adult lung alveolar organoid formation
2021
Introduction: IL11 was recently reported to induce the formation of myofibroblasts and their secretion of collagen, while its subcutaneous administration drives the development of pulmonary fibrosis in mice. Less is known as to how IL11 affects epithelial-mesenchymal communication associated with epithelial repair, and regarding which cell types are the main producers and responders to IL11 in vivo. Here we aim to investigate the role of IL11 in alveolar regeneration. Methods: Epithelial progenitor cell behavior was studied using an organoid model, comprised of a co-culture of primary mouse CD31-CD45-Epcam+ cells with either CCL206 fibroblasts or primary human fibroblasts. After 14 days, the number and size of the organoids were determined, and immunofluorescent staining for Surfactant protein C (SPC) and acetylated tubulin (ACT) was performed to define alveolar vs airway organoids. Immunohistochemical staining of IL11 and IL11R was performed on human lung tissue to observe producer and responder cells of IL11 signaling. Results: The presence of rhIL11 significantly decreased the number of both mouse and human organoids formed in a concentration-dependent manner, and the fraction of SPC+ organoids was reduced by rhIL11 whereas the fraction of SPC-ACT- organoids was increased. Organoid size was not affected. Finally, immunohistochemistry revealed that IL11R is found in smooth muscle, airway epithelium and endothelium, whereas IL11 was primarily observed in airway epithelium, alveolar type 2 cells and macrophages. Conclusions: IL11 may impair epithelial progenitor function by suppressing their activation and by suppressing the formation of mature alveolar cell types. IL11R localization suggests mesenchymal activation by IL11 may contribute to observed effects on progenitor function.
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