Regulatory eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis

Andreev D, Liu M, Kachler K, Llerins Perez M, Kirchner P, Kölle J, Gießl A, Rauber S, Song R, Aust O, Grüneboom A, Kleyer A, Cañete JD, Ekici AB, Ramming A, Finotto S, Schett G, Bozec A (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

DOI: 10.1136/annrheumdis-2020-218902

Abstract

Objectives: Eosinophils possess pro-inflammatory functions in asthma. However, our recent studies have suggested that innate lymphoid cells type 2 (ILC2s) and eosinophils have proresolving properties in rheumatoid arthritis (RA). Nothing is known yet about the mechanisms determining the double-edged role of eosinophils. Therefore, we investigated whether asthma, a paradigm eosinophilic disease, can elicit resolution of chronic arthritis. Methods: Ovalbumin-triggered eosinophilic asthma was combined with K/BxN serum-induced arthritis, where lung and synovial eosinophil subsets were compared by single-cell RNA sequencing (scRNA-seq). To investigate the involvement of the ILC2-interleukin-5 (IL-5) axis, hydrodynamic injection (HDI) of IL-25 and IL-33 plasmids, IL-5 reporter mice and anti-IL-5 antibody treatment were used. In patients with RA, the presence of distinct eosinophil subsets was examined in peripheral blood and synovial tissue. Disease activity of patients with RA with concomitant asthma was monitored before and after mepolizumab (anti-IL-5 antibody) therapy. Results: The induction of eosinophilic asthma caused resolution of murine arthritis and joint tissue protection. ScRNA-seq revealed a specific subset of regulatory eosinophils (rEos) in the joints, distinct from inflammatory eosinophils in the lungs. Mechanistically, synovial rEos expanded on systemic upregulation of IL-5 released by lung ILC2s. Eosinophil depletion abolished the beneficial effect of asthma on arthritis. rEos were consistently present in the synovium of patients with RA in remission, but not in active stage. Remarkably, in patients with RA with concomitant asthma, mepolizumab treatment induced relapse of arthritis. Conclusion: These findings point to a hitherto undiscovered proresolving signature in an eosinophil subset that stimulates arthritis resolution.

Authors with CRIS profile

Darja Andreev Department of Medicine 3 – Rheumatology and Immunology Mengdan Liu Professur für Experimentelle Immuntherapie Julia Kölle Department of Molecular Pneumology Andreas Gießl Department of Ophthalmology Simon Rauber Department of Medicine 3 – Rheumatology and Immunology Rui Song Department of Medicine 3 – Rheumatology and Immunology Arnd Kleyer Lehrstuhl für Innere Medizin III Arif Bülent Ekici Lehrstuhl für Humangenetik Andreas Ramming Medizinische Fakultät Susetta Neurath-Finotto Department of Molecular Pneumology Georg Schett Lehrstuhl für Innere Medizin III Aline Bozec Professur für Experimentelle Immuntherapie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

J076: The role of itaconate-mediated metabolic reprogramming in osteoclasts Oct. 16, 2019 - April 15, 2022

Involved external institutions

Hospital Clínic de Barcelona ES Spain (ES)

How to cite

APA:

Andreev, D., Liu, M., Kachler, K., Llerins Perez, M., Kirchner, P., Kölle, J.,... Bozec, A. (2020). Regulatory eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis. Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2020-218902

MLA:

Andreev, Darja, et al. "Regulatory eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis." Annals of the Rheumatic Diseases (2020).

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