RT Journal Article
SR Electronic
T1 Regulatory eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 451
OP 468
DO 10.1136/annrheumdis-2020-218902
VO 80
IS 4
A1 Darja Andreev
A1 Mengdan Liu
A1 Katerina Kachler
A1 Mireia Llerins Perez
A1 Philipp Kirchner
A1 Julia Kölle
A1 Andreas Gießl
A1 Simon Rauber
A1 Rui Song
A1 Oliver Aust
A1 Anika Grüneboom
A1 Arnd Kleyer
A1 Juan D Cañete
A1 Arif Ekici
A1 Andreas Ramming
A1 Susetta Finotto
A1 Georg Schett
A1 Aline Bozec
YR 2021
UL http://ard.bmj.com/content/80/4/451.abstract
AB 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.