Potential involvement of OX40 in the regulation of autoantibody sialylation in arthritis
| العنوان: | Potential involvement of OX40 in the regulation of autoantibody sialylation in arthritis |
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| المؤلفون: | Ayako Ohyama, Yuya Kondo, Shunta Kaneko, Isao Matsumoto, Izumi Kurata, Takayuki Sumida, Azusa Tomioka, Hiroshi Ebe, Hoshimi Kawaguchi, Atsumu Osada, Hiroto Tsuboi, Hiroyuki Kaji |
| المصدر: | Annals of the Rheumatic Diseases. 78:1488-1496 |
| بيانات النشر: | BMJ, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Immunology, Arthritis, General Biochemistry, Genetics and Molecular Biology, Arthritis, Rheumatoid, Mice, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, In vivo, Follicular phase, Animals, Immunology and Allergy, Medicine, B cell, Autoantibodies, Immunity, Cellular, biology, business.industry, Autoantibody, T-Lymphocytes, Helper-Inducer, Receptors, OX40, medicine.disease, In vitro, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Mice, Inbred DBA, Rheumatoid arthritis, Sialic Acids, biology.protein, Antibody, business, 030215 immunology |
| الوصف: | ObjectiveAn increased proportion of circulating follicular helper T (Tfh) cells was reported in rheumatoid arthritis (RA), but it remains uncertain how Tfh cells affect antibody hyposialylation. We investigated the regulation of autoantibody hyposialylation by Tfh cells in RA using murine model.MethodsBehaviours of Tfh cells and their function on B cell promotion were analysed. Change of arthritogenicity and sialylation of autoantibodies during the course of arthritis was examined by mass spectrometry. Tfh-mediated regulation of hyposialylation was investigated, and the responsible cell surface molecule was specified both in vitro and in vivo. The relation between circulating Tfh cells and hyposialylation was analysed in patients with RA.ResultsAn increase in Tfh, particularly interleukin-17 producing Tfh (Tfh17) cells, at the onset of arthritis and their enhancement of autoantibody production were found. Autoantibodies at the onset phase demonstrated stronger inflammatory properties than those at the resolution phase, and mass spectrometric analysis revealed their difference in sialylation. In vitro coculture showed enhanced hyposialylation by the Tfh cells via OX40, which was highly expressed in the Tfh and Tfh17 cells. Blockade of OX40 prevented the development of arthritis with reduction in Tfh17 cells and recovery of autoantibody sialylation. Analysis of patients with RA showed abundance of OX40-overexpressing Tfh17 cells, and their proportion correlated negatively with the expression of α2,6-sialyltransferase 1, an enzyme responsible for sialylation.ConclusionsOX40 expressed on Tfh cells can regulate autoantibody sialylation and play a crucial role in the development of autoimmune arthritis. |
| تدمد: | 1468-2060 0003-4967 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::330fff0566b287b876ae7794d16c8719Test https://doi.org/10.1136/annrheumdis-2019-215195Test |
| رقم الانضمام: | edsair.doi.dedup.....330fff0566b287b876ae7794d16c8719 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682060 00034967 |
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