Interleukin-36 family dysregulation drives joint inflammation and therapy response in psoriatic arthritis
| العنوان: | Interleukin-36 family dysregulation drives joint inflammation and therapy response in psoriatic arthritis |
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| المؤلفون: | Myles Lewis, Katriona Goldmann, Costantino Pitzalis, Gloria Lliso-Ribera, Edoardo Prediletto, Giulia Maria Ghirardi, Alessandra Nerviani, Marie-Astrid Boutet, Davide Lucchesi |
| المصدر: | Rheumatology (Oxford, England) |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | rheumatoid arthritis, musculoskeletal diseases, 0301 basic medicine, Oncology, medicine.medical_specialty, Biopsy, medicine.medical_treatment, Gene Expression, Arthritis, interleukin-36, In Vitro Techniques, urologic and male genital diseases, early arthritis, Arthritis, Rheumatoid, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Rheumatology, Psoriasis, Synovitis, Internal medicine, Humans, Medicine, Pharmacology (medical), RNA, Messenger, skin and connective tissue diseases, psoriatic arthritis, Inflammation, 030203 arthritis & rheumatology, business.industry, Interleukins, Arthritis, Psoriatic, Synovial Membrane, Clinical Science, medicine.disease, Synoviocytes, cytokines, Prostate-specific antigen, 030104 developmental biology, medicine.anatomical_structure, Cytokine, Antirheumatic Agents, Rheumatoid arthritis, Synovial membrane, synovitis, business, Interleukin-1 |
| الوصف: | Objectives IL-36 agonists are pro-inflammatory cytokines involved in the pathogenesis of psoriasis. However, their role in the pathogenesis of arthritis and treatment response to DMARDs in PsA remains uncertain. Therefore, we investigated the IL-36 axis in the synovium of early, treatment-naïve PsA, and for comparison RA patients, pre- and post-DMARDs therapy. Methods Synovial tissues were collected by US-guided biopsy from patients with early, treatment-naïve PsA and RA at baseline and 6 months after DMARDs therapy. IL-36 family members were investigated in synovium by RNA sequencing and immunohistochemistry, and expression levels correlated with DMARDs treatment response ex vivo. Additionally, DMARDs effects on IL-36 were investigated in vitro in fibroblast-like synoviocytes. Results PsA synovium displayed a reduced expression of IL-36 antagonists, while IL-36 agonists were comparable between PsA and RA. Additionally, neutrophil-related molecules, which drive a higher activation of the IL-36 pathway, were upregulated in PsA compared with RA. At baseline, the synovial expression of IL-36α was significantly higher in PsA non-responders to DMARDs treatment, with the differential expression being sustained at 6 months post-treatment. In vitro, primary PsA-derived fibroblasts were more responsive to IL-36 stimulation compared with RA and, importantly, DMARDs treatment increased IL-36 expression in PsA fibroblasts. Conclusion The impaired balance between IL-36 agonists–antagonists described herein for the first time in PsA synovium and the decreased sensitivity to DMARDs in vitro may explain the apparent lower efficacy of DMARDs in PsA compared with RA. Exogenous replacement of IL-36 antagonists may be a novel promising therapeutic target for PsA patients. |
| تدمد: | 1462-0332 1462-0324 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa1547103aec23bfdbf70775b76667cfTest https://doi.org/10.1093/rheumatology/kez358Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....aa1547103aec23bfdbf70775b76667cf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14620332 14620324 |
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