TLR-7 and -9 Stimulation of Peripheral Blood B Cells Indicate Altered TLR Signalling in Primary Sjögren's Syndrome Patients by Increased Secretion of Cytokines.
Primary Sjögren's syndrome (pSS) is a chronic, inflammatory autoimmune disease characterised by lymphocytic infiltrations in the exocrine glands, resulting in destruction of salivary and lacrimal glands. B cells have an important role in the disease, as detection of autoantibodies against SSA/Ro or SSB/La is one of the diagnostic criteria, being found in a majority of the patients. Toll-like receptors (TLR) are pattern recognition receptors. TLR-7 and -9 are found in endosomes and bind microbial nucleic acids. We have previously shown that pSS patients and healthy controls have similar expression pattern of TLR-7 and -9 in various B-cell populations. In this study we further analysed the responsiveness of B cells upon TLR stimulation. B cells isolated from peripheral blood of 21 pSS patients and 18 healthy controls were stimulated with TLR-7 and -9 ligands for 24 h before being analysed for the expression of certain surface markers and intracellular cytokine levels by flow cytometry. Secreted cytokines were measured by a multiplex cytokine assay. Patients with pSS had more naïve and less preswitched memory B cells compared to controls in unstimulated as well as via TLR-7 stimulated cells. Unstimulated and via TLR-7 stimulated B cells from pSS patients also had fewer IL-10(+) preswitched memory B cells. Moreover, TLR-7 and -9 stimulated B cells of pSS patients secreted increased amounts of several cytokines. B cells of pSS patients show a different responsiveness upon stimulation of TLR-7 and -9 compared to controls.
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
M
M
Karlsen
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
R
R
Jonsson
Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
J G
JG
Brun
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
S
S
Appel
Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.
T
T
Hansen
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D055815:Young Adult
D016207:Cytokines; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9