CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis

Rauber S, Mohammadian H, Schmidkonz C, Atzinger A, Soare A, Treutlein C, Kemble S, Mahony CB, Geisthoff M, Angeli MR, Raimondo MG, Xu C, Yang KT, Lu L, Labinsky H, Saad Msa, Anchang CG, Chang J, Huang K, Kampylafka E, Knitza J, Bilyy R, Distler J, Hanlon MM, Fearon U, Veale DJ, Roemer F, Bäuerle T, Maric HM, Maschauer S, Ekici AB, Buckley CD, Croft AP, Kuwert T, Prante O, Cañete JD, Schett G, Ramming A (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Nature Immunology Nature Research

DOI: 10.1038/s41590-024-01774-4

Abstract

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). Spatial transcriptomics of human joints indicates that pro-resolving niches of CD200+DKK3+ fibroblasts cluster with type 2 innate lymphoid cells, whereas MMP3+/IL6+ fibroblasts colocalize with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilized the type 2 innate lymphoid cell phenotype and induced resolution of arthritis via CD200–CD200R1 signaling. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

Authors with CRIS profile

Simon Rauber Department of Medicine 3 – Rheumatology and Immunology Hashem Mohammadian Department of Medicine 3 – Rheumatology and Immunology Christian Schmidkonz Medizinische Fakultät Armin Atzinger Department of Nuclear Medicine Christoph Treutlein Institute of Radiology Mario Raphael Angeli Department of Medicine 3 – Rheumatology and Immunology Maria Gabriella Raimondo Department of Medicine 3 – Rheumatology and Immunology Cong Xu Department of Medicine 3 – Rheumatology and Immunology Kai-Ting Yang Department of Medicine 3 – Rheumatology and Immunology Le Lu Department of Medicine 3 – Rheumatology and Immunology Hannah Labinsky Department of Medicine 3 – Rheumatology and Immunology Mina saad aziz Saad Department of Medicine 3 – Rheumatology and Immunology Charles Gwellem Anchang Department of Medicine 3 – Rheumatology and Immunology Jiyang Chang Department of Medicine 3 – Rheumatology and Immunology Kaiyue Huang Professur für Molekulare Mechanismen der Organfibrose Johannes Knitza Department of Medicine 3 – Rheumatology and Immunology Jörg Distler Professur für Molekulare Mechanismen der Organfibrose Frank Roemer Institute of Radiology Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Simone Maschauer Department of Nuclear Medicine Arif Bülent Ekici Institute of Human Genetics Torsten Kuwert Lehrstuhl für Klinische Nuklearmedizin Olaf Prante Medizinische Fakultät Georg Schett Lehrstuhl für Innere Medizin III Andreas Ramming Professur für Immunologie der Organschädigung

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung (IZKF) FAU Forschungszentrum Neue Wirkstoffe (FAU NeW)

Involved external institutions

University of Oxford GB United Kingdom (GB) Hospital Clínic de Barcelona ES Spain (ES) University of Birmingham GB United Kingdom (GB) St Vincent's University Hospital IE Ireland (IE) Trinity College Dublin IE Ireland (IE) Danylo Halytsky Lviv National Medical University / Львiвський Національний Медичний Унiверситет iм. Данила Галицького UA Ukraine (UA) Julius-Maximilians-Universität Würzburg DE Germany (DE)

How to cite

APA:

Rauber, S., Mohammadian, H., Schmidkonz, C., Atzinger, A., Soare, A., Treutlein, C.,... Ramming, A. (2024). CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis. Nature Immunology. https://doi.org/10.1038/s41590-024-01774-4

MLA:

Rauber, Simon, et al. "CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis." Nature Immunology (2024).

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