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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.

ObjectiveWe aimed to evaluate changes in the contrast-enhanced ultrasound (CEUS) parameters in patients with idiopathic retroperitoneal fibrosis (RPF) before and after treatment, and to analyse the value of CEUS to assess RPF activity. MethodsWe performed a prospective study that included patients with idiopathic RPF who were treated for RPF at our hospital from April 2016 to April 2019. All patients underwent CEUS examination and some of them underwent positron emission tomography/computed tomography (PET/CT) examination simultaneously. CEUS parameters included tube wall and peripheral thickness, arterial wall intensity, and lumen intensity. The changes in CEUS parameters before and after treatment were evaluated, and their correlations with the standardised uptake value (SUVmax), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed. ResultsThirty-one active idiopathic RPF patients were enrolled, of whom 11 underwent PET/CT examination before treatment.Tube wall and peripheral thickness (r=0.743, p<0.01) and arterial wall intensity (r=0.702, p<0.05) both correlated significantly with SUVmax. Lumen intensity did not correlate significantly with SUVmax (r=0.544, p=0.084). The correlation coefficients between lesion thickness and ESR levels were 0.508 (p=0.037), between lesion thickness and CRP levels were 0.575 (p=0.016). Arterial wall intensity and lumen intensity were not significantly correlated with ESR or CPR levels. Tube wall and peripheral thickness, arterial wall intensity, decreased significantly after treatment (p=0.001), while the lumen intensity was not significantly changed after treatment. ConclusionOur findings suggest that CEUS, a radiation-free and repeatable detection method, is effective for assessing idiopathic RPF disease activity.