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TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines
bioRxiv - Immunology Pub Date : 2020-05-27 , DOI: 10.1101/2020.05.24.113167
Nadine Honke , Torsten Lowin , Birgit Opgenoorth , Namir Shaabani , Alexander Lautwein , John R. Teijaro , Matthias Schneider , Georg Pongratz

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 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. 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.

中文翻译:

TLR9激活的B细胞通过内源产生的儿茶酚胺改善其调节功能

交感神经系统(SNS)通过促进抗炎性B细胞促进免疫平衡。然而,对于B细胞是否具有调节其调节性B细胞(Breg)功能的自我调节机制尚不清楚。在这项研究中,我们调查了B细胞在用不同的B细胞激活剂刺激后合成儿茶酚胺的能力。我们发现,产生儿茶酚胺所需的酶的表达被TLR9上调。酪氨酸羟化酶(TH)的TLR-9特异性表达与肾上腺素受体的上调,增强的IL-10产生以及共抑制性配体PD-L1和FasL的过表达有关。此外,交感神经系统(SNS)的伴随刺激通过促进抗炎性B细胞促进免疫平衡。然而,B细胞是否具有自我调节机制来调节调节性B细胞(Breg)功能尚不清楚。在这项研究中,我们调查了B细胞在用不同的B细胞激活剂刺激后合成儿茶酚胺的能力。我们发现,产生儿茶酚胺所需的酶的表达被TLR9上调。酪氨酸羟化酶(TH)的TLR-9特异性表达与肾上腺素受体的上调,增强的IL-10产生以及共抑制性配体PD-L1和FasL的过表达有关。此外,β1-3-肾上腺素能受体的伴随刺激与BCR / TLR9刺激一起增强了Bregs抑制CD4 T细胞的抗炎能力,CD4 T细胞是自身免疫疾病(如类风湿关节炎)发病机理中的关键人群。结论,我们的数据表明B细胞具有调节其调节功能的自主机制。这些发现有助于更好地了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。β1-3-肾上腺素能受体与BCR / TLR9刺激一起增强Breg抑制CD4 T细胞的抗炎能力,CD4 T细胞是自身免疫性疾病(如类风湿关节炎)发病机理中的关键人群。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了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。这些发现有助于更好地了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。Beta 1-3-肾上腺素能受体与BCR / TLR9刺激一起增强Breg抑制CD4 T细胞的抗炎能力,CD4 T细胞是自身免疫性疾病(如类风湿关节炎)发病机理中的关键人群。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了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。这些发现有助于更好地了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。Beta 1-3-肾上腺素能受体与BCR / TLR9刺激一起增强Breg抑制CD4 T细胞的抗炎能力,CD4 T细胞是自身免疫性疾病(如类风湿关节炎)发病机理中的关键人群。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了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。Beta 1-3-肾上腺素能受体与BCR / TLR9刺激一起增强Breg抑制CD4 T细胞的抗炎能力,CD4 T细胞是自身免疫性疾病(如类风湿关节炎)发病机理中的关键人群。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了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。Beta 1-3-肾上腺素能受体与BCR / TLR9刺激一起增强Breg抑制CD4 T细胞的抗炎能力,CD4 T细胞是自身免疫性疾病(如类风湿关节炎)发病机理中的关键人群。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了解Bregs在自身免疫性疾病中的功能以及交感神经系统与B细胞功能的相互作用。
更新日期:2020-05-27
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