Extracellular matrix - immune system interaction

细胞外基质-免疫系统相互作用

• 批准号: 188485349
• 负责人: Professor Dr. Bent Brachvogel
• 金额: --
• 依托单位: Klinik und Poliklinik für Kinder- und Jugendmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/188485349?language=en
• 关键词: Extracellular; matrix; immune; system; interaction

The extracellular matrix (ECM) of the bone marrow is derived from a secreted specialized matrix in growth plate cartilage. Changes in the composition of the cartilage ECM early in development can affect the organization of the ECM in the bone marrow to impair the development and function of bone marrow derived immune cells, but little is known about the underlying mechanisms. Collagen IX is expressed in cartilage to stabilize the ECM. Our recent findings show that lack of collagen IX transiently alters the composition of the trabecular ECM in the postnatal bone marrow to impair myeloid progenitor cell differentiation in the adult. In the planned project we will identify proteins of the ECM in collagen IX deficient mice that can induce long term changes in hematopoiesis. Protein interaction studies will be used to characterize the interplay of these proteins with the cartilage ECM and extracellular signaling molecules, while cell culture differentiation assays and infection studies in collagen IX deficient mice will define their influence on hematopoiesis and the immune response. The analysis will characterize the priming effects of cartilage ECM components on immune cell differentiation and function. Moreover, the results may provide a general understanding of ECM induced immune-related diseases of the skeletal system.

骨髓的细胞外基质（ECM）来源于生长板软骨中分泌的特化基质。软骨ECM在发育早期的组成变化可影响骨髓中ECM的组织化，从而损害骨髓源性免疫细胞的发育和功能，但对其潜在机制知之甚少。胶原IX在软骨中表达以稳定ECM。我们最近的研究结果表明，缺乏胶原IX短暂改变组成的小梁细胞外基质在出生后的骨髓损害髓系祖细胞分化的成年人。在计划的项目中，我们将确定蛋白质的ECM在胶原IX缺陷小鼠，可以诱导长期的变化，造血。蛋白质相互作用研究将用于表征这些蛋白质与软骨ECM和细胞外信号分子的相互作用，而胶原IX缺陷小鼠中的细胞培养分化测定和感染研究将确定它们对造血和免疫应答的影响。该分析将表征软骨ECM组分对免疫细胞分化和功能的引发作用。此外，该结果可能提供ECM诱导的骨骼系统免疫相关疾病的一般理解。

项目成果

Depletion of Collagen IX Alpha1 Impairs Myeloid Cell Function

• DOI: 10.1002/stem.2892
• 发表时间: 2018-09
• 期刊: STEM CELLS
• 影响因子: 5.2
• 作者: K. Probst;J. Stermann;Inga von Bomhard;J. Etich;Lena Pitzler;A. Niehoff;Björn Bluhm;Haifeng C. Xu;P. Lang;M. Chmielewski;H. Abken;Birgit Blissenbach;A. Machova;N. Papadopoulou;B. Brachvogel

Bedeutung der extrazellulären Matrix des Knorpels für die Entwicklung und Funktion des Immunsystems

软骨细胞外基质对免疫系统发育和功能的重要性

• DOI: 10.1007/s00393-015-1650-x
• 发表时间: 2015
• 期刊: Zeitschrift für Rheumatologie
• 作者: Etich J;Brachvogel B
• 通讯作者: Brachvogel B