Skin-derived myeloid precursors and joint-resident fibroblasts spread psoriatic disease from skin to joints
Maria G. Raimondo, Hashem Mohammadian, Mario R. Angeli, Stefano Alivernini, Vladyslav Fedorchenko, Kaiyue Huang, Richard Demmler, Peter Rhein, Cong Xu, Yi-Nan Li, Raphael Micheroli, Zoltán Winter, Aleix Rius Rigau, Charles Gwellem Anchang, Alina Soare, Markus Luber, Hannah Labinsky, Jiyang Chang, Claudia Günther, Ursula Fearon, Douglas J. Veale, Francesco Ciccia, Jürgen Rech, Michael Sticherling, Tobias Doyle Bäuerle, Jörg H W Distler, Mariola S. Kurowska-Stolarska, Matthias Mack, A Ekici, Adam P. Croft, Oliver Distler, Hans Maric, Caroline Ospelt, Juan D. Cañete, Maria A. D’Agostino, Georg Schett, Simon Rauber, Andreas Ramming
Abstract
Abstract Psoriatic disease initially affects the skin and later extends to the joints. Here, we show a two-step process that orchestrates the spread of inflammation from the skin to the joints. Induction of psoriatic skin disease in photoconvertible mice, followed by sequencing and computational characterization of skin-derived cells in the joints, was used to identify a population of CD2 + MHC-II + CCR2 + myeloid precursors that builds a skin-derived myeloid cell compartment in the joints. Single-cell cross-species reference mapping and mitochondrial variant tracing showed an orthologous human cell population. Interactome analysis of the joints showed that in a second step, resident regulatory CD200 + fibroblasts regulate the priming of CD2 + MHC-II + CCR2 + myeloid precursors, which subsequently control IL-17 expression in T cells. Hence, the spread of inflammation requires a distinct migratory myeloid precursor population and a permissive local tissue environment, similar to tumor metastasis.