title: IL-7 receptor α expressing B cells act proinflammatory in collagen-induced arthritis and are inhibited by sympathetic neurotransmitters.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, , Regensburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Pongratz
authors.forename: Judith M
authors.initials: JM
authors.lastname: Anthofer
authors.forename: Madlen
authors.initials: M
authors.lastname: Melzer
authors.forename: Sven
authors.initials: S
authors.lastname: Anders
authors.forename: Susanne
authors.initials: S
authors.lastname: Grässel
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009638:Norepinephrine / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013564:Sympathetic Nervous System / Q000276:immunology* / Q000378:metabolism; D013566:Sympathomimetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D015851:Interleukin-7; D008070:Lipopolysaccharides; D020395:Receptors, Interleukin-7; D013566:Sympathomimetics; C576410:interleukin-7, mouse; D006854:Hydrocortisone; D009638:Norepinephrine
keywords: Arthritis; B cells; Rheumatoid Arthritis