Endogenously produced catecholamines improve the regulatory function of TLR9-activated B cells
Autor: | Nadine Honke, Torsten Lowin, Birgit Opgenoorth, Namir Shaabani, Alexander Lautwein, John R. Teijaro, Matthias Schneider, Georg Pongratz |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: | |
Zdroj: | PLoS Biology, Vol 20, Iss 1 (2022) |
Druh dokumentu: | article |
ISSN: | 1544-9173 1545-7885 |
Popis: | 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 their own catecholamines upon stimulation with different B cell activators and found that expression of the enzyme tyrosine hydroxylase (TH), required to generate catecholamines, is up-regulated by Toll-like receptor (TLR)9. This TLR9-dependent expression of TH correlated with up-regulation of adrenergic receptors (ADRs), enhanced interleukin (IL)-10 production, and overexpression of the co-inhibitory ligands programmed death ligand 1 (PD-L1) and Fas ligand (FasL). Moreover, concomitant stimulation of ß1-3-ADRs together with a B cell receptor (BCR)/TLR9 stimulus clearly enhances the anti-inflammatory potential of Bregs to suppress CD4 T cells, a crucial population in the pathogenesis of autoimmune diseases, like rheumatoid arthritis (RA). Furthermore, TH up-regulation was also demonstrated in B cells during the course of collagen-induced arthritis (CIA), a mouse model for the investigation of RA. In conclusion, our data show that B cells possess an autonomous mechanism to modulate their regulatory function in an autocrine and/or paracrine manner. These findings help to better understand the function of B cells in the regulation of autoimmune diseases and the interplay of SNS. The sympathetic nervous system produces neurotransmitters such as catecholamines which contribute to immune balance by promoting anti-inflammatory B cells. This study shows that mouse B cells can themselves synthesize, sense, and transport catecholamines, which in turn modulate regulatory B cell function in an autocrine and/or paracrine manner to suppress T cell proliferation. |
Databáze: | Directory of Open Access Journals |
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