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The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis
  1. Georg Pongratz,
  2. Madlen Melzer,
  3. Rainer H Straub
  1. Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
  1. Correspondence to Georg Pongratz, Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany; georg.pongratz{at}klinik.uni-regensburg.de

Abstract

Background As previously shown, the sympathetic nervous system (SNS) shows proinflammatory activity during initiation of arthritis but is anti-inflammatory in established collagen-induced arthritis (CIA). Interleukin 10 (IL-10)-producing B cells suppress arthritis and are a potential target of the SNS because (1) B cells express functional β2-adrenoceptors (β2ARs) and (2) IL-10, at least in monocytes/macrophages, is regulated in a cAMP/PKA/CREB-dependent manner.

Objective To test the hypothesis that anti-inflammatory effects of the SNS in CIA are mediated by stimulating IL-10-producing anti-inflammatory B cells.

Methods Collagen-induced arthritis in DBA/1 mice, sympathectomy, adoptive B cell transfer, in vitro B cell culture, and assessment of B cell IL-10 production.

Results and conclusion Mice treated with B cells from SNS-intact mice showed less severe arthritis than mice treated with B cells from sympathectomised mice. This anti-inflammatory action of B cells from SNS-intact mice correlated with increased IL-10 produced by B cells, which was mediated by norepinephrine (NE), in a β2AR, PKA-dependent manner. However, an NE-mediated increase in IL-10 was seen only in B cells from immunised but not naive mice, explaining in part the anti-inflammatory properties of the SNS in the late phase of arthritis. Finally, animals treated with B cells isolated from immunised mice and activated in vitro in the presence of a β2AR stimulus showed a decrease in arthritis severity in comparison with controls, an approach that might be used for future cellular treatment strategies.

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Footnotes

  • Funding This study was funded by the institution and by the Deutsche Forschungsgemeinschaft (DFG FOR696, PO801/4-1).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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