IL-7 receptor α expressing B cells act proinflammatory in collagen-induced arthritis and are inhibited by sympathetic neurotransmitters
- Georg Pongratz1,
- Judith M Anthofer1,
- Madlen Melzer1,
- Sven Anders2,
- Susanne Grässel3,
- Rainer H Straub1
- 1Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
- 2Deptartment of Orthopaedic Surgery, University Hospital Regensburg, Asklepios Clinic Bad Abbach, Bad Abbach, Germany
- 3Experimental Orthopedics, ZMB/BioPark1; University Hospital Regensburg, Regensburg, Germany
- Correspondence to Dr Georg Pongratz, Laboratory of Exp. Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, Regensburg 93042, Germany;
- Accepted 24 February 2013
- Published Online First 16 March 2013
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-7Rα is increased when B cells are activated (anti-CD40 or lipopolysaccharide) in vitro and stimulating the IL-7R induces intracellular accumulation of pSTAT5. α- And β-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 β2-adreonceptor (β2AR) agonist terbutaline. IL-7R and β2AR 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.