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bioRxiv · 10.1101/2020.05.24.113167

TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines

Honke, N.·Lowin, T.·Opgenoorth, B.·Shaabani, N.·Lautwein, A.·Teijaro, J. R.·Schneider, M.·Pongratz, G.
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Abstract

The sympathetic nervous system (SNS) contributes to immune balance by promoting anti-inflammatory B cells. However, whether B cells possess a self-regulating mechanism by which they modulate regulatory B cell (Breg) function is not well understood. In this study, we investigated the ability of B cells to synthesize catecholamines upon stimulation with different B cell activators. We found, that expression of the enzymes required to generate catecholamines, is upregulated by TLR9. TLR-9-specific expression of tyrosine hydroxylase (TH) correlated with upregulation of adrenergic receptors, enhanced IL-10 production, and with an overexpression of the co-inhibitory ligands PD-L1 and FasL. Moreover, concomitant stimulation of {beta}1-3-adrenergic receptors together with a BCR/TLR9 stimulus enhances the anti-inflammatory potential of Bregs to suppress CD4 T cells, a crucial population in the pathogenesis of autoimmune diseases, like rheumatoid arthritis. In conclusion, our data show that B cells possess autonomous mechanisms to modulate their regulatory function. These findings help to better understand the function of Bregs in autoimmune diseases and the interplay of sympathetic nervous system and B cell function.

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Honke, N., Lowin, T., Opgenoorth, B., Shaabani, N., Lautwein, A., Teijaro, J. R., Schneider, M., Pongratz, G.. 2020-05-27. TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines. https://doi.org/10.1101/2020.05.24.113167

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