Pongratz, Georg and Anthofer, Judith M. and Melzer, Madlen and Anders, Sven and Graessel, Susanne and Straub, Rainer H. (2014) IL-7 receptor alpha expressing B cells act proinflammatory in collagen-induced arthritis and are inhibited by sympathetic neurotransmitters. ANNALS OF THE RHEUMATIC DISEASES, 73 (1). pp. 306-312. ISSN 0003-4967, 1468-2060
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Objectives The sympathetic nervous system (SNS) as well as the interleukin (IL)-7/IL-7 receptor (IL-7R) system play a role in the pathogenesis of arthritis. However, the target cells and mechanisms involved are not fully resolved. The goal of this study was to determine if B cells are influenced by IL-7 and to investigate the possible interplay between the SNS and the IL-7/IL-7R system on B cells in arthritis. Methods Collagen type II-induced arthritis (CIA) in DBA1 mice. ELISA to determine specific anti-CII antibodies. Fluorescence activated cell sorting (FACS) analysis to determine IL-7R+ cells and intracellular phosphorylated signal transducer and activator of transcription 5 (pSTAT5). Immunohistochemistry to show IL-7R+ B cells in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Results IL-7 stimulated IL-7R+ mature B cells act proinflammatory (increased clinical score, increased anticollagen type II antibodies) after cell transfer in CIA. The sympathetic neurotransmitter norepinephrine abrogates this effect. Expression of IL-7R is increased when B cells are activated (anti-CD40 or lipopolysaccharide) in vitro and stimulating the IL-7R induces intracellular accumulation of pSTAT5. - And -adrenergic agonists show no influence on expression levels of IL-7R on activated B cells; however, intracellular IL-7R downstream signalling is abrogated via the 2-adreonceptor (2AR) agonist terbutaline. IL-7R and 2AR are also expressed on B cells in synovial tissue from RA and OA patients. Conclusions These data indicate that IL7R+ B cells have a proinflammatory role in arthritis which can be inhibited by the sympathetic neurotransmitter norepinephrine via inhibition of IL-7R signalling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RHEUMATOID-ARTHRITIS; INTERLEUKIN-7 RECEPTOR; BONE-MARROW; IN-VIVO; T-CELL; NOREPINEPHRINE RELEASE; SYNOVIAL TISSUE; NERVE FIBERS; ACTIVATION; CHAIN; Arthritis; B cells; Rheumatoid Arthritis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Dec 2019 15:07 |
| Last Modified: | 03 Dec 2019 15:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/11123 |
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