Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
- Rheumatoid arthritis (RA) is an autoimmune disease in which next to other cell populations CD4 T cells play a crucial role. It has been shown that catecholamines provided by the sympathetic nervous system (SNS) ameliorate the development and course of arthritis by increasing the production of the anti-inflammatory cytokine IL-10 in regulatory B cells (Bregs). In the current study, we investigated whether Bregs have the ability to produce catecholamines and how such a production is regulated. Moreover, we tested which adrenergic receptor activation is important to improve the Bregs function to evaluate if an additional adrenergic receptor stimulus can enhance the suppression of CD4 T cells.
- In in vitro experiments on activated murine B cells or B cells and splenocytes from collagen-induced arthritis (CIA) mice, modulation of Bregs and their effect on CD4 T cells proliferation were investigated. The production and release of catecholamines were analyzed in naïve, IgM, CpG or IgM/CpG activated B cells after 4h and 24h by FACS. For analysis of CD4 T cell suppression pre-inactivated or pre-activated B cells and CD3/CD28 activated splenocytes from immunized mice were cocultured for 48h and 72 h. CD4 T cell proliferation as well as the expression of PDL-1 and Fas-L on B cells was monitored by FACS. The IL-10 production from B cells was directly measured in the cells by intracellular FACS staining or in the supernatant of B cell cultures by ELISA.
Results: Catecholamines are not only provided by the SNS but are produced by the B cells themselves. Analysis of B cells by FACS showed a raised production of catecholamines after short time exposure to different B cell activation stimuli (Control vs. IgM, n=6, n.s.; Control vs. CpG, n=6, p***< 0,0002; Control vs. IgM/CpG, n= 6, p****< 0,0001). Long time activation of B cells, on the other hand, leads to release of produced catecholamines (Control vs. IgM, n=4, p**< 0,0029; Control vs. CpG, n=4, p****< 0,0001; Control vs. IgM/CpG, n= 4, p****< 0,0001). This hints to a time and context dependent production and release of catecholamines. Furthermore, FACS analysis showed that CpG-activated Bregs have the ability to suppress CD4 T cells (Control vs. CpG, n= 11, p****< 0,0001). Increased suppression of CD4 T cells was observed after addition of norepinephrine or isoproterenol, ADR beta agonists, to CpG-activated Bregs (CpG vs. CpG/NE, n=11, p*=0,0343; CpG vs. CpG/Iso, n=11, p***=0,0009). This higher suppression of CD4 T cells correlates with enhanced IL-10 production by Bregs (CpG vs. CpG+Iso, n=8, % rel. to control ~40%, p**=0,0045; CpG vs. CpG+NE, n=8, % rel. to control ~16%, p**=0,0012).
Conclusion: In conclusion, our data suggest that ß-adrenergic receptor activation by catecholamines or synthethic receptor agonists in addition to a BCR/TLR9 stimulus is associated with an increase of the anti-inflammatory potential of regulatory B cells to suppress CD4 T cells. This could be a strategy to modulate Bregs for therapeutic purposes in RA.
To cite this abstract in AMA style:Honke N, Opgenoorth B, Schneider M, Pongratz G. ß-adrenergic Receptor Activation: A Way to Enhance CD4 T Cell Suppression by Improving Regulatory B Cell Function [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/s-adrenergic-receptor-activation-a-way-to-enhance-cd4-t-cell-suppression-by-improving-regulatory-b-cell-function/. Accessed June 5, 2020.
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