%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.