Interleukin-13 disrupts type 2 pneumocyte stem cell activity
Kristen M. Glisinski, Adam J. Schlobohm, Sarah V. Paramore, Anastasiya Birukova, M. Arthur Moseley, Matthew W. Foster, Christina E. Barkauskas
Kristen M. Glisinski, Adam J. Schlobohm, Sarah V. Paramore, Anastasiya Birukova, M. Arthur Moseley, Matthew W. Foster, Christina E. Barkauskas
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Research Article Pulmonology Stem cells

Interleukin-13 disrupts type 2 pneumocyte stem cell activity

Abstract

The T helper 2 (Th2) inflammatory cytokine interleukin-13 (IL-13) has been associated with both obstructive and fibrotic lung diseases; however, its specific effect on the epithelial stem cells in the gas exchange compartment of the lung (alveolar space) has not been explored. Here, we used in vivo lung models of homeostasis and repair, ex vivo organoid platforms, and potentially novel quantitative proteomic techniques to show that IL-13 disrupts the self-renewal and differentiation of both murine and human type 2 alveolar epithelial cells (AEC2s). Significantly, we find that IL-13 promotes ectopic expression of markers typically associated with bronchiolar airway cells and commonly seen in the alveolar region of lung tissue from patients with idiopathic pulmonary fibrosis. Furthermore, we identify a number of proteins that are differentially secreted by AEC2s in response to IL-13 and may provide biomarkers to identify subsets of patients with pulmonary disease driven by “Th2-high” biology.

Authors

Kristen M. Glisinski, Adam J. Schlobohm, Sarah V. Paramore, Anastasiya Birukova, M. Arthur Moseley, Matthew W. Foster, Christina E. Barkauskas

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Figure 6

Human lung cell culture.

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Human lung cell culture. (A) Schematic for processing of normal human lu...
(A) Schematic for processing of normal human lung for culture of hAEC2s. (B) Representative example of human alveolospheres grown with and without IL-13. (C) CFE is similar with and without IL-13, but average sphere diameter is higher in IL-13–treated cultures. (D) Quantification of cell number per unit circumference. The cells in IL-13–treated spheres cover more surface area and appear elongated. Two-tailed t test; error bars represent mean ± SD. (E) Representative immunohistochemistry of AEC2s (HTII-280+) and AEC1s (AQP5+) in human alveolospheres grown with and without IL-13. Note the morphology of IL-13–treated spheres is different from controls and there is less staining for both AEC2 and AEC1 markers. There are more proliferating (MKI67+) cells in the IL-13–treated organoids. Two-tailed t test; error bars represent mean ± SD. (F) Representative spheres from a separate donor. Note larger diameter of IL-13–treated sphere and less expression of the AEC2 marker, SFTPC. One-way ANOVA; error bars represent mean ± SD. Dot colors correspond to separate donors. Donors are listed as HLT-xxx. Scale bars: 500 μm (B), 60 μm (D), 50 μm (E), 30 μm (F). *P < 0.05; **P < 0.005.