dc.creator | Mavropoulos A., Simopoulou T., Varna A., Liaskos C., Katsiari C.G., Bogdanos D.P., Sakkas L.I. | en |
dc.date.accessioned | 2023-01-31T08:58:10Z | |
dc.date.available | 2023-01-31T08:58:10Z | |
dc.date.issued | 2016 | |
dc.identifier | 10.1002/art.39437 | |
dc.identifier.issn | 23265191 | |
dc.identifier.uri | http://hdl.handle.net/11615/76444 | |
dc.description.abstract | Objective Breg cells, a regulatory cell subset that produces interleukin-10 (IL-10), play a significant role in suppressing autoimmune responses and preventing autoimmunity. This study was undertaken to examine the number and function of Breg cells in patients with systemic sclerosis (SSc), a disease with many autoantibodies. Methods Forty-five patients with SSc (12 with early SSc, 33 with established disease including 16 with SSc-associated pulmonary fibrosis [PF]), 12 healthy control subjects, and 10 patients with rheumatoid arthritis (RA)-associated PF were studied. The phenotypes of immature/transitional Breg cells (CD19+CD24highCD38high) and memory Breg cells (CD19+CD27+CD24high) were evaluated by flow cytometry. The function of Breg cells was assessed by measuring the production of IL-10 after B cell activation. In addition, activation of p38 MAPK and STAT-3 was measured following stimulation of the cells with B cell receptor (BCR) and Toll-like receptor 9 (TLR-9). Results Percentages of memory Breg cells were decreased in patients with early SSc (mean ± SEM 1.85 ± 0.38%), those with established SSc (1.6 ± 0.88%), those with SSc-associated PF (1.52 ± 0.17%), and those with RA-associated PF (1.58 ± 0.26%), compared to healthy controls (6.3 ± 0.49%; each P < 0.001). Percentages of transitional Breg cells were also decreased. Expression of IL-10 by Breg cells after stimulation with TLR-9 was impaired in patients with SSc, particularly those with SSc-associated PF. Activation of STAT-3 and p38 MAPK was impaired in naive and memory B cells from patients with SSc after stimulation with BCR and TLR-9. Expression of the stimulatory CD19 receptor was increased in B cells and also increased, to a lesser extent, in Breg cells from patients with SSc compared to healthy controls. Percentages of memory B cells were decreased in patients with SSc, particularly in those with SSc-associated PF. Conclusion This is the first study to demonstrate that Breg cells are phenotypically and functionally impaired in patients with SSc. Furthermore, in SSc, B cells exhibit impaired p38 MAPK and STAT-3 activation upon stimulation with BCR and TLR-9. The findings of decreased numbers of Breg cells along with increased expression of CD19 support the idea of B cell autoaggression acting as an immunopathogenic mediator in SSc. © 2016, American College of Rheumatology. | en |
dc.language.iso | en | en |
dc.source | Arthritis and Rheumatology | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84956737145&doi=10.1002%2fart.39437&partnerID=40&md5=5ee3666b65d6c5a69afcf5923d5a55bb | |
dc.subject | CD19 antigen | en |
dc.subject | CD24 antigen | en |
dc.subject | CD27 antigen | en |
dc.subject | CD38 antigen | en |
dc.subject | IL10 protein, human | en |
dc.subject | interleukin 10 | en |
dc.subject | lymphocyte antigen receptor | en |
dc.subject | mitogen activated protein kinase p38 | en |
dc.subject | STAT3 protein | en |
dc.subject | STAT3 protein, human | en |
dc.subject | toll like receptor 9 | en |
dc.subject | adult | en |
dc.subject | aged | en |
dc.subject | B lymphocyte | en |
dc.subject | case control study | en |
dc.subject | complication | en |
dc.subject | female | en |
dc.subject | flow cytometry | en |
dc.subject | human | en |
dc.subject | immunology | en |
dc.subject | lymphocyte activation | en |
dc.subject | lymphocyte count | en |
dc.subject | male | en |
dc.subject | middle aged | en |
dc.subject | Pulmonary Fibrosis | en |
dc.subject | rheumatoid arthritis | en |
dc.subject | severity of illness index | en |
dc.subject | systemic sclerosis | en |
dc.subject | Adult | en |
dc.subject | Aged | en |
dc.subject | Antigens, CD19 | en |
dc.subject | Antigens, CD24 | en |
dc.subject | Antigens, CD27 | en |
dc.subject | Antigens, CD38 | en |
dc.subject | Arthritis, Rheumatoid | en |
dc.subject | B-Lymphocytes, Regulatory | en |
dc.subject | Case-Control Studies | en |
dc.subject | Female | en |
dc.subject | Flow Cytometry | en |
dc.subject | Humans | en |
dc.subject | Interleukin-10 | en |
dc.subject | Lymphocyte Activation | en |
dc.subject | Lymphocyte Count | en |
dc.subject | Male | en |
dc.subject | Middle Aged | en |
dc.subject | p38 Mitogen-Activated Protein Kinases | en |
dc.subject | Pulmonary Fibrosis | en |
dc.subject | Receptors, Antigen, B-Cell | en |
dc.subject | Scleroderma, Systemic | en |
dc.subject | Severity of Illness Index | en |
dc.subject | STAT3 Transcription Factor | en |
dc.subject | Toll-Like Receptor 9 | en |
dc.subject | John Wiley and Sons Inc. | en |
dc.title | Breg Cells Are Numerically Decreased and Functionally Impaired in Patients with Systemic Sclerosis | en |
dc.type | journalArticle | en |