Anti-inflammatory pathways of catecholaminergic, tyrosine hydroxylase (TH) - positive cells in human and experimental arthritis

人类和实验性关节炎中儿茶酚胺能酪氨酸羟化酶 (TH) 阳性细胞的抗炎途径

• 批准号: 243785207
• 负责人: Professor Dr. Rainer H. Straub
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/243785207?language=en
• 关键词: Anti; inflammatory; pathways; catecholaminergic; tyrosine

In inflamed synovial tissue of patients and mice, tyrosine hydroxylase (TH) - positive cells (TH+ cells) were discovered in previous work in the applicant s group. These cells have a strong anti-inflammatory potential as described by the applicant s group in patients with rheumatoid arthritis (RA) and osteoarthritis. In recent work within Research Unit, mesenchymal stem cell (MSC) - derived TH+ cells had strong anti-inflammatory effects in the model of experimental collagen type II -induced arthritis. However, the exact sympathetic signalling pathway (whether adrenergic, dopaminergic, or purinergic [i.e., adenosine]) or the specific target cell of these sympathetic TH+ cells are not known.This project will delineate the sympathetic pathway responsible for anti-inflammatory effects of primary and MSC-derived TH+ cells using cell material of patients with RA / OA and arthritic mice. This project will also reveal the target cell responsible for anti-inflammatory effects in humans and mice. Knowledge of the sympathetic pathway will be used to treat animals with experimental arthritis in order to fully characterize the clinical ameliorating effect of TH+ cells. Finally, sympathetic differentiation techniques are applied to human lymphocytes of patients with RA to generate TH+ lymphocytes. These differentiated cells can be used as a platform for a cell-based therapy (use of MSC-derived TH+ cells or TH+ lymphocytes to treat RA).

在患者和小鼠的发炎滑膜组织中，在申请人小组的先前工作中发现了酪氨酸羟化酶（TH）阳性细胞（TH+细胞）。如申请人的小组在类风湿性关节炎（RA）和骨关节炎患者中所描述的，这些细胞具有强的抗炎潜力。在最近的研究中，间充质干细胞（MSC）衍生的TH+细胞在实验性II型胶原诱导的关节炎模型中具有强烈的抗炎作用。然而，确切的交感神经信号传导途径（无论是肾上腺素能、多巴胺能还是嘌呤能[即，本项目将使用RA / OA患者和关节炎小鼠的细胞材料描绘负责原代和MSC衍生的TH+细胞的抗炎作用的交感神经通路。该项目还将揭示负责人类和小鼠抗炎作用的靶细胞。交感神经通路的知识将用于治疗患有实验性关节炎的动物，以充分表征TH+细胞的临床改善作用。最后，将交感神经分化技术应用于RA患者的人淋巴细胞以产生TH+淋巴细胞。这些分化的细胞可以用作基于细胞的治疗（使用MSC衍生的TH+细胞或TH+淋巴细胞来治疗RA）的平台。

项目成果

A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells

• DOI: 10.1159/000495349
• 发表时间: 2018-12
• 期刊: Neuroimmunomodulation
• 影响因子: 2.4
• 作者: M. Ebbinghaus;Z. Jenei-Lanzl;G. Segond von Banchet;H. Stangl;M. Gajda;R. Straub;H. Schaible

Proinflammatory receptor switch from Gαs to Gαi signaling by β-arrestin-mediated PDE4 recruitment in mixed RA synovial cells

• DOI: 10.1016/j.bbi.2015.07.020
• 发表时间: 2015-11-01
• 期刊: BRAIN BEHAVIOR AND IMMUNITY
• 影响因子: 15.1
• 作者: Jenei-Lanzl, Zsuzsa;Zwingenberg, Janika;Straub, Rainer H.
• 通讯作者: Straub, Rainer H.