%A Kadefors,Måns %A Berlin,Frida %A Wildt,Marie %A Dellgren,Göran %A Rolandsson Enes,Sara %A Aspberg,Anders %A Westergren-Thorsson,Gunilla %D 2022 %J Frontiers in Pharmacology %C %F %G English %K fibroblast,Lung,Fibrosis,Idiopathic Pulmonary Fibrosis,Dipeptidyl Peptidase 4 %Q %R 10.3389/fphar.2022.953771 %W %L %M %P %7 %8 2022-August-31 %9 Original Research %# %! DPP4 and lung fibroblast phenotype %* %< %T Dipeptidyl peptidase 4 expression is not associated with an activated fibroblast phenotype in idiopathic pulmonary fibrosis %U https://www.frontiersin.org/articles/10.3389/fphar.2022.953771 %V 13 %0 JOURNAL ARTICLE %@ 1663-9812 %X Dipeptidyl peptidase 4 (DPP4) has been proposed as a marker for activated fibroblasts in fibrotic disease. We aimed to investigate whether a profibrotic DPP4 phenotype is present in lung tissue from patients with idiopathic pulmonary fibrosis (IPF). The presence of DPP4+ fibroblasts in normal and IPF lung tissue was investigated using flow cytometry and immunohistology. In addition, the involvement of DPP4 in fibroblast activation was examined in vitro, using CRISPR/Cas9 mediated genetic inactivation to generate primary DPP4 knockout lung fibroblasts. We observed a reduced frequency of primary DPP4+ fibroblasts in IPF tissue using flow cytometry, and an absence of DPP4+ fibroblasts in pathohistological features of IPF. The in vivo observations were supported by results in vitro showing a decreased expression of DPP4 on normal and IPF fibroblasts after profibrotic stimuli (transforming growth factor β) and no effect on the expression of activation markers (α-smooth muscle actin, collagen I and connective tissue growth factor) upon knockout of DPP4 in lung fibroblasts with or without activation with profibrotic stimuli.