Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
The Sympathetic Neurotransmitter Norepinephrine Inhibits Proinflammatory IL-7-Receptor Alpha Positive B Cells in Arthritis.
Pongratz, Georg, Anthofer, Judith, Melzer, Madlen, Straub, Rainer H.
Recent data show higher concentrations of IL-7 in synovial fluid of patients with rheumatoid arthritis (RA) as compared to osteoarthritis (OA). Among other cells in the inflamed synovium, IL-7 receptor (IL-7R) is expressed on synovial B cells but the role of these cells in arthritis is unclear.
Collagen type II induced arthritis (CIA) in DBA1 mice. ELISA to determine specific anti-CII antibodies. Isolation of naïve splenic B cells and in vitro culture. FACS analysis to determine IL-7R+ cells and intracellular pSTAT5. Immunohistochemistry to show pSTAT5+ and IL-7R+ B cells in RA and OA synovial tissue.
Activation of naïve splenic murine B cells with CD40L and IL-4 in vitro increases IL-7R expression. To determine the role of IL-7R+ B cells in arthritis we treated arthritic mice with B cells that have been activated and stimulated with IL-7. Mice treated with IL-7 stimulated B cells developed more severe arthritis than controls. We also show that human RA and OA tissue contains IL-7R+ and pSTAT5+ B cells in synovial tissue. We know from former experiments that norepinephrine treated B cells show anti-inflammatory potential in arthritis. Therefore, B cells were activated in the presence of norepinehphrine and then stimulated with IL-7. Treatment of mice with these B cells did not show different severity of arthritis as compared to controls. As possible explanation for this observation we show that proper IL-7R signaling via STAT5 is inhibited in B cells pretreated with norepinephrine.
Taken together, 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 signaling.
To cite this abstract, please use the following information:
Pongratz, Georg, Anthofer, Judith, Melzer, Madlen, Straub, Rainer H.; The Sympathetic Neurotransmitter Norepinephrine Inhibits Proinflammatory IL-7-Receptor Alpha Positive B Cells in Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1754