Academic Journal
Augmented Th17 Differentiation Leads to Cutaneous and Synovio‐Entheseal Inflammation in a Novel Model of Psoriatic Arthritis
| العنوان: | Augmented Th17 Differentiation Leads to Cutaneous and Synovio‐Entheseal Inflammation in a Novel Model of Psoriatic Arthritis |
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| المؤلفون: | Yang, Lu, Fanok, Melania H., Mediero‐Munoz, Aranzazu, Fogli, Laura K., Corciulo, Carmen, Abdollahi, Shahla, Cronstein, Bruce N., Scher, Jose U., Koralov, Sergei B. |
| المساهمون: | National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Instituto de Salud Carlos III, Arthritis Foundation |
| المصدر: | Arthritis & Rheumatology ; volume 70, issue 6, page 855-867 ; ISSN 2326-5191 2326-5205 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2018 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Objective To introduce a novel preclinical animal model of psoriatic arthritis (PsA) in R26Stat3C stopfl/fl CD4Cre mice, and to investigate the role of Th17 cytokines in the disease pathogenesis. Methods We characterized a novel murine model of Th17‐driven cutaneous and synovio‐entheseal disease directed by T cell–specific expression of a hyperactive Stat3 allele. By crossing R26Stat3C stopfl/fl CD4Cre mice onto an interleukin‐22 (IL‐22)–knockout background or treating the mice with a neutralizing antibody against IL‐17, we interrogated how these Th17 cytokines could contribute to the pathogenesis of PsA. Results R26Stat3C stopfl/fl CD4Cre mice developed acanthosis, hyperkeratosis, and parakeratosis of the skin, as well as enthesitis/tendinitis and periarticular bone erosion in different joints, accompanied by osteopenia. T cell–specific expression of a hyperactive Stat3C allele was found to drive the augmented Th17 response in these animals. Careful characterization of the mouse bone marrow revealed an increase in osteoclast progenitor (OCP) and RANKL‐producing cells, which contributed to the osteopenia phenotype observed in the mutant animals. Abrogation of the Th17 cytokines IL‐17 or IL‐22 improved both the skin and bone phenotype in R26Stat3C stopfl/fl CD4Cre mice, revealing a central role of Th17 cells in the regulation of OCP and RANKL expression on stromal cells. Conclusion Perturbation of the IL‐23/Th17 axis instigates Th17‐mediated inflammation in R26Stat3C stopfl/fl CD4Cre mice, leading to cutaneous and synovio‐entheseal inflammation and bone pathologic features highly reminiscent of human PsA. Both IL‐17A and IL‐22 produced by Th17 cells appear to play critical roles in promoting the cutaneous and musculoskeletal inflammation that characterizes PsA. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/art.40447 |
| الاتاحة: | http://dx.doi.org/10.1002/art.40447 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fart.40447 https://onlinelibrary.wiley.com/doi/full/10.1002/art.40447 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.67D4C3A2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/art.40447 |
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