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ObjectivesEosinophils 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.MethodsOvalbumin-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.ResultsThe 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.ConclusionThese findings point to a hitherto undiscovered proresolving signature in an eosinophil subset that stimulates arthritis resolution.

The use of microscopes for the study of immune cells dates back to the 19th century with the German Pathologist Rudolf Virchow being one of the most prominent leaders in the field early on. It was him who coined the term "Zellularpathologie" (cellular pathology 1 ), while the famous concept associated with this theory, "omnis cellula e cellula" (all cells are derived from previous cells) was probably not originally from him. 2 Virchow was one of the earliest who observed by microscopy that inflammatory cells isolated from a punctured hydrocele were motile. Considering the inflammatory condition where they were harvested from and when looking at the images in his publication it might well be that he was looking at neutrophil granulocytes or macrophages at the time. 3 Hence, this could be the first description of the motility of these cells. More well-known are the famous studies by the Ukranian scientist Ilya Metchnikoff 20 years