TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines
TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines
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DOI：
10.1101/2020.05.24.113167
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发表时间：
2020-05
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通讯作者：
N. Honke;T. Lowin;B. Opgenoorth;Namir Shaabani;Alexander Lautwein;J. Teijaro;Matthias Schneider;G. Pongratz
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作者：
N. Honke;T. Lowin;B. Opgenoorth;Namir Shaabani;Alexander Lautwein;J. Teijaro;Matthias Schneider;G. Pongratz
交感神经系统（SNS）通过促进抗炎B细胞而有助于免疫平衡。然而，B细胞是否具有调节调节B细胞（布雷格）功能的自我调节机制尚不清楚。在这项研究中，我们调查的能力，B细胞合成儿茶酚胺刺激后，不同的B细胞活化剂。我们发现，产生儿茶酚胺所需的酶的表达被TLR 9上调。酪氨酸羟化酶（TH）的TLR-9特异性表达与肾上腺素能受体的上调、IL-10产生的增强以及共抑制配体PD-L1和FasL的过表达相关。此外，β 1 -3-肾上腺素能受体的伴随刺激与BCR/TLR 9刺激一起增强了BcR抑制CD 4 T细胞的抗炎潜力，CD 4 T细胞是自身免疫性疾病如类风湿性关节炎发病机制中的关键群体。总之，我们的数据表明，B细胞具有自主机制来调节其调节功能。这些发现有助于更好地理解Bcl 2在自身免疫性疾病中的作用以及交感神经系统和B细胞功能的相互作用。
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 ß1-3-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.