Karlsen, M.;
Jonsson, R.;
Brun, J. G.;
Appel, S.;
Hansen, T.
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
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Media type:
E-Article
Title:
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
Contributor:
Karlsen, M.;
Jonsson, R.;
Brun, J. G.;
Appel, S.;
Hansen, T.
Published:
Wiley, 2015
Published in:
Scandinavian Journal of Immunology, 82 (2015) 6, Seite 523-531
Description:
<jats:title>Abstract</jats:title><jats:p>Primary Sjögren's syndrome (<jats:styled-content style="fixed-case">pSS</jats:styled-content>) 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 <jats:styled-content style="fixed-case">SSA</jats:styled-content>/Ro or <jats:styled-content style="fixed-case">SSB</jats:styled-content>/La is one of the diagnostic criteria, being found in a majority of the patients. Toll‐like receptors (<jats:styled-content style="fixed-case">TLR</jats:styled-content>) are pattern recognition receptors. <jats:styled-content style="fixed-case">TLR</jats:styled-content>‐7 and ‐9 are found in endosomes and bind microbial nucleic acids. We have previously shown that <jats:styled-content style="fixed-case">pSS</jats:styled-content> patients and healthy controls have similar expression pattern of <jats:styled-content style="fixed-case">TLR</jats:styled-content>‐7 and ‐9 in various B‐cell populations. In this study we further analysed the responsiveness of B cells upon <jats:styled-content style="fixed-case">TLR</jats:styled-content> stimulation. B cells isolated from peripheral blood of 21 <jats:styled-content style="fixed-case">pSS</jats:styled-content> patients and 18 healthy controls were stimulated with <jats:styled-content style="fixed-case">TLR</jats:styled-content>‐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 <jats:styled-content style="fixed-case">pSS</jats:styled-content> had more naïve and less preswitched memory B cells compared to controls in unstimulated as well as via <jats:styled-content style="fixed-case">TLR</jats:styled-content>‐7 stimulated cells. Unstimulated and via <jats:styled-content style="fixed-case">TLR</jats:styled-content>‐7 stimulated B cells from <jats:styled-content style="fixed-case">pSS</jats:styled-content> patients also had fewer <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10<jats:sup>+</jats:sup> preswitched memory B cells. Moreover, <jats:styled-content style="fixed-case">TLR</jats:styled-content>‐7 and ‐9 stimulated B cells of <jats:styled-content style="fixed-case">pSS</jats:styled-content> patients secreted increased amounts of several cytokines. B cells of <jats:styled-content style="fixed-case">pSS</jats:styled-content> patients show a different responsiveness upon stimulation of <jats:styled-content style="fixed-case">TLR</jats:styled-content>‐7 and ‐9 compared to controls.</jats:p>