Promotion of regulatory B cell function by catecholamines - implications for autoimmune arthritis

儿茶酚胺促进调节性 B 细胞功能 - 对自身免疫性关节炎的影响

• 批准号: 323627809
• 负责人: Professor Dr. Georg Pongratz
• 金额: --
• 依托单位: Krankenhaus Barmherzige Brüder Regensburg
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/323627809?language=en
• 关键词: Promotion; regulatory; cell; function; catecholamines

Main goal of the project is a better understanding of the modulation of regulatory B cells by catecholamines to derive new treatment targets for autoimmunity, with a focus on autoimmune arthritis. It is known that catecholamines, wich are provided in the microenvironment by the sympathetic nervous system or catecholamine producing, tyrosin hydroxylase (TH) positive cells, are modulators of autoimmune diseases. Adrenergic receptors, especially beta-2 adrenoceptors, which are expressed on almost all immune cells, directly mediate this regulation. We could show in recent work in a model of rheumatoid arthritis (collagen-induced arthritis in mice) that catecholamines via acting on regulatory B cells (increase in IL-10) show anti-inflammatory properties and improve arthritis. In the proposed project we want to investigate, which catecholaime-dependent mechanisms lead to an increase in regulatory B cell function, if these mechanisms can be targeted to influence regulatory B cell function, if these mechanisms are also established in the human system, and if they are pathophysiologically relevant. If we succeed in better understanding and manipulating these mechanisms this would provide us with a means to develop novel treatment strategies, especially for rheumatoid arthritis, along with a better understanding of regulatory B cell physiology. However, results from this project might play a broader role for inflammatory diseases, where regulatory B cells are involved in pathophysiology.

该项目的主要目标是更好地了解儿茶酚胺对调节性 B 细胞的调节，以得出自身免疫的新治疗靶点，重点关注自身免疫性关节炎。众所周知，儿茶酚胺是由交感神经系统或产生儿茶酚胺的酪氨酸羟化酶(TH)阳性细胞在微环境中提供的，是自身免疫性疾病的调节剂。肾上腺素能受体，尤其是 β2 肾上腺素受体，几乎在所有免疫细胞上表达，直接介导这种调节。我们最近在类风湿性关节炎（小鼠胶原诱导的关节炎）模型中的研究表明，儿茶酚胺通过作用于调节性 B 细胞（IL-10 增加）显示出抗炎特性并改善关节炎。在拟议的项目中，我们想要研究哪些儿茶酚依赖性机制导致调节性 B 细胞功能增强，这些机制是否可以有针对性地影响调节性 B 细胞功能，这些机制是否也在人体系统中建立，以及它们是否具有病理生理学相关性。如果我们成功地更好地理解和操纵这些机制，这将为我们提供一种开发新的治疗策略的方法，特别是对于类风湿性关节炎，同时更好地理解调节性 B 细胞生理学。 然而，该项目的结果可能在炎症性疾病中发挥更广泛的作用，调节性 B 细胞参与病理生理学。

项目成果

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

• DOI: 10.1101/2020.05.24.113167
• 发表时间: 2020-05
• 期刊: bioRxiv
• 作者: N. Honke;T. Lowin;B. Opgenoorth;Namir Shaabani;Alexander Lautwein;J. Teijaro;Matthias Schneider;G. Pongratz

Introduction and validation of a new semi-automated method to determine sympathetic fiber density in target tissues

• DOI: 10.1371/journal.pone.0217475
• 发表时间: 2019-05-29
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Bleck, Dennis;Ma, Li;Pongratz, Georg
• 通讯作者: Pongratz, Georg