Crosstalk between fibrotic alveolar basal cells and lung fibroblasts: Effects on differentiation and mediator expression

<bold>Rationale:</bold> Ectopic alveolar basal cells (BC) accumulate within in the lung parenchyma of interstitial lung disease (ILD) patients. Crosstalk between ectopic alveolar BC and resident lung fibroblasts may contribute to fibrogenesis. Therefore, we investigated the interaction between fibrotic alveolar BC and lung fibroblasts in an in vitro co-culture model. <bold>Methods:</bold> BC and fibroblasts were isolated from fibrotic or non-fibrotic peripheral lung tissue. BC were cultured on cell culture inserts and fibroblasts in 12-well culture plates and maintained as mono- or co-cultures under submerged or air liquid interface (ALI) culture conditions. Effects on specific cell markers or mediators was analyzed by immunofluorescence, TaqMan PCR or ELISA. <bold>Results:</bold> When cultured on an ALI for 21 days, alveolar BC differentiated to SCGB1A1+ and MUC5B+ secretory and ciliated (FOXJ1, AcTub) epithelial cells, which was accompanied by an up-regulation of MMP7. In the presence of fibrotic or non-fibrotic fibroblasts, MUC5B, SCGB1A1, and FOXJ1 expression significantly further increased, whereas that of MMP7 decreased. Vice versa, fibrotic and non-fibrotic fibroblasts expressed less Col1A1 and α-SMA and more MMP1 when co-cultured with alveolar BC for 24 hours. <bold>Conclusions:</bold> Our in vitro data suggest that paracrine interactions between alveolar BC and lung fibroblasts enhance BC mucociliary differentiation, but may not contribute to enhanced collagen deposition by fibroblasts or their differentiation to myofibroblasts. Further studies are needed to get a deeper understanding of BC-fibroblast interactions and its potential contribution to fibrogenesis.