Simon Rauber, Hashem Mohammadian, Christian Schmidkonz, Armin Atzinger, Alina Soare, Christoph Treutlein, Samuel Kemble, Christopher B Mahony, Manuel Geisthoff, Mario R Angeli, Maria G Raimondo, Cong Xu, Kai-Ting Yang, Le Lu, Hannah Labinsky, Mina S A Saad, Charles A Gwellem, Jiyang Chang, Kaiyue Huang, Eleni Kampylafka, Johannes Knitza, Rostyslav Bilyy, Jörg H W Distler, Megan M Hanlon, Ursula Fearon, Douglas J Veale, Frank W Roemer, Tobias Bäuerle, Hans M Maric, Simone Maschauer, Arif B Ekici, Christopher D Buckley, Adam P Croft, Torsten Kuwert, Olaf Prante, Juan D Cañete, Georg Schett, Andreas Ramming
Fibroblasts are important regulators of inflammation, but whether fibroblasts change phenotype during resolution of inflammation is not clear. Here we use positron emission tomography to detect fibroblast activation protein (FAP) as a means to visualize fibroblast activation in vivo during inflammation in humans. While tracer accumulation is high in active arthritis, it decreases after tumor necrosis factor and interleukin-17A inhibition. Biopsy-based single-cell RNA-sequencing analyses in experimental arthritis show that FAP signal reduction reflects a phenotypic switch from pro-inflammatory MMP3+ /IL6+ fibroblasts (high FAP internalization) to pro-resolving CD200+ DKK3+ fibroblasts (low FAP internalization)...
February 23, 2024: Nature Immunology