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45. Kongress der Deutschen Gesellschaft für Rheumatologie, 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

06.09. - 09.09.2017, Stuttgart

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Activation in vivo and in vitro increases responsiveness to catecholamines and regulatory potential of B cells by increasing IL-10 in a p38- and Gi-dependent manner

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  • Georg Pongratz - Universitätsklinikum Düsseldorf, Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, Düsseldorf
  • Katharina Krebber - Universitätsklinikum Düsseldorf, Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, Düsseldorf
  • Rainer H. Straub - University Hospital Regensburg, Lab. of Exp. Rheumatology & Neuroendocrine Immunology, Regensburg
  • Matthias Schneider - Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
  • Torsten Lowin - Universitätsklinikum Düsseldorf, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, Düsseldorf

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Stuttgart, 06.-09.09.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocER.20

doi: 10.3205/17dgrh089, urn:nbn:de:0183-17dgrh0897

Published: September 4, 2017

© 2017 Pongratz et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Background: Splenic B cells from collagen-induced arthritis (CIA) mice react to a beta2-adrenoceptor (AR) stimulus with increased IL-10 production and adoptive transfer of these cells decreases disease activity. However, B cells from unimmunized mice do not adequately increase IL-10. Therefore, we test the hypothesis that sensitivity to catecholamines changes during CIA and try to mimick changes that have to occur in vivo, in the in vitro setting with the goal to increase regulatory potential of B cells in vitro.

Methods: FACS, ELISA, Western Blot, human and mouse B cell culture, CIA

Results: In the course of CIA the percentage of beta2-AR+ B cells increased (ANOVA p<0.05), G-protein coupled receptor kinase (GRK2) decreased from day 6 p.i. (ANOVA p<0.0001), and phosphorylation of p38 (ANOVA p<0.001) and cAMP-responsive element binding protein (CREB, ANOVA p<0.001) following a beta2-AR stimulus is augmented in late CIA. Responsiveness to catecholamines can also be increased in vitro by unspecific, T cell independent stimuli to naive murine B cells, which increases ARs and leads to increased, p38-dependent IL-10 production. Interestingly, the catecholamine induced IL-10 increase can be blocked by pertussis toxin, a Gi Protein antagonist, pointing to beta-arrestin rather than cAMP-dependent mechanism.

Conclusion: The current data show, that B cells increase catecholamine responsiveness via increased AR and downregulated GRK2 in the course of CIA and after T cell independent activation, favoring p38-dependent and Gi-dependent mechanisms that increase IL-10. Defining key players in this complex regulatory mechanisms might lead to new therapeutic strategies in autoimmune diseases.