Endogenously produced catecholamines improve the regulatory function of TLR9-activated B cells.
Endogenously produced catecholamines improve the regulatory function of TLR9-activated B cells.
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DOI：
10.1371/journal.pbio.3001513
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发表时间：
2022-01
期刊：
影响因子：
9.8
通讯作者：
Pongratz G
中科院分区：
文献类型：
--
作者：
Honke N;Lowin T;Opgenoorth B;Shaabani N;Lautwein A;Teijaro JR;Schneider M;Pongratz G
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，我们研究了B细胞的能力，合成自己的儿茶酚胺刺激后，与不同的B细胞活化剂，发现酪氨酸羟化酶（TH）的表达，需要产生儿茶酚胺，上调Toll样受体（TLR）9。TH的这种TLR 9依赖性表达与肾上腺素能受体（ADR）的上调、增强的白细胞介素（IL）-10产生以及共抑制配体程序性死亡配体1（PD-L1）和Fas配体（FasL）的过表达相关。此外，β 1 -3-ADR的伴随刺激与B细胞受体（BCR）/TLR 9刺激一起明显增强了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（RA）发病机制中的关键群体。此外，TH的上调也表现在B细胞的过程中胶原诱导的关节炎（CIA），RA的研究小鼠模型。总之，我们的数据表明，B细胞具有自主机制，以自分泌和/或旁分泌的方式调节其调节功能。这些发现有助于更好地理解B细胞在自身免疫性疾病的调节中的功能以及SNS的相互作用。交感神经系统产生神经递质，例如通过促进抗炎B细胞而有助于免疫平衡的儿茶酚胺。这项研究表明，小鼠B细胞本身可以合成，感觉和运输儿茶酚胺，这反过来又调节调节B细胞功能的自分泌和/或旁分泌的方式，以抑制T细胞增殖。
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.
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DOI：
10.1016/j.bbi.2018.09.004
发表时间：
2018-11
期刊：
Brain, behavior, and immunity
影响因子：
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DOI：
10.1073/pnas.0811139106
发表时间：
2008-12-23
影响因子：
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