cd19+cd24hicd38hi b cells are expanded in juvenile dermatomyositis and exhibit a pro-inflammatory phenotype after activation through toll-like receptor 7 and interferon-α
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2018
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Abstract
Juvenile dermatomyositis (JDM) is a rare form of childhood autoimmune myositis that presents with proximal muscle weakness and skin rash. B cells are strongly implicated in the pathogenesis of the disease, but the underlying mechanisms are unknown. Therefore, the main objective of our study was to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in JDM patients. Patients were recruited through the UK JDM Cohort and Biomarker study. Peripheral blood B cell subpopulations were immunophenotyped by flow cytometry. The results identified that immature transitional B cells were significantly expanded in active JDM, actively dividing, and correlated positively with disease activity. Protein and RNAseq analysis revealed high interferon alpha (IFNα) and TLR7-pathway signatures pre-treatment. Stimulation of B cells through TLR7/8 promoted both IL-10 and IL-6 production in controls but failed to induce IL-10 in JDM patient cells. Interrogation of the CD40–CD40L pathway (known to induce B cell IL-10 and IL-6) revealed similar expression of IL-10 and IL-6 in B cells cultured with CD40L from both JDM patients and controls. In conclusion, JDM patients with active disease have a significantly expanded immature transitional B cell population which correlated with the type I IFN signature. Activation through TLR7 and IFNα may drive the expansion of immature transitional B cells in JDM and skew the cells toward a pro-inflammatory phenotype.
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| Authors | ;Christopher J. M. Piper;Meredyth G. Ll. Wilkinson;Meredyth G. Ll. Wilkinson;Claire T. Deakin;Claire T. Deakin;Claire T. Deakin;Georg W. Otto;Georg W. Otto;Stefanie Dowle;Stefanie Dowle;Chantal L. Duurland;Stuart Adams;Emiliano Marasco;Elizabeth C. Rosser;Anna Radziszewska;Anna Radziszewska;Rita Carsetti;Yiannis Ioannou;Yiannis Ioannou;Philip L. Beales;Philip L. Beales;Daniel Kelberman;Daniel Kelberman;David A. Isenberg;David A. Isenberg;Claudia Mauri;Kiran Nistala;Lucy R. Wedderburn;Lucy R. Wedderburn;Lucy R. Wedderburn |
| Journal | sudebno-meditsinskaia ekspertiza |
| Year | 2018 |
| DOI |
10.3389/fimmu.2018.01372
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