Role for the bone environment in regulating immune responses

骨环境在调节免疫反应中的作用

• 批准号: 168985739
• 负责人: Dr. Jean-Pierre David, Ph.D. (†)
• 金额: --
• 依托单位: Institut für Osteologie und Biomechanik (IOBM)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/168985739?language=en
• 关键词: Role; bone; environment; regulating; immune

Bone harboring bone marrow is the main hematopoietic organ in adults. It provides the local environment for maintenance and recruitment of the hematopoietic stem cells from which all hematopoietic cells differentiate. In addition, it provides a niche for B cell development and long lived plasma cells, thereby, maintaining humoral memory. Up to now the role of lymphocytes on bone homeostasis has been a main focus of research in osteoimmunology. Pro-inflammatory T cells (TH1 and TH17) were shown to promote bone destruction whereas T-regulatory cells (TReg) and B cells protect against inflammation-induced bone loss. While it is clear that lymphocytes are actively involved in bone remodeling, the role of the bone in regulating immunity has been poorly addressed. It is well known that the reduction of the bone marrow space observed in osteopetrosis or osteosclerosis induces secondary extramedullary hematopoisis in liver and spleen due to a changed bone marrow environment. Whether alterations of bone homeostasis also affect adaptive immunity is less known. Hence, we want to analyze the consequences of osteosclerosis and osteopetrosis on adaptive immune responses to determine whether the lymphocyte development in the bone marrow is essential for the development of a competent immune system.

骨髓是成人主要的造血器官。它提供了维持和募集造血干细胞的局部环境，所有的造血细胞都是从这个环境中分化出来的。此外，它为B细胞的发育和长寿的浆细胞提供了一个生态位，从而维持了体液记忆。迄今为止，淋巴细胞在骨稳态中的作用一直是骨免疫学研究的主要热点。促炎T细胞（TH1和TH17）可促进骨破坏，而T调节细胞（TReg）和B细胞可防止炎症诱导的骨质流失。虽然淋巴细胞积极参与骨重塑是很清楚的，但骨在调节免疫中的作用却很少得到解决。众所周知，在骨质疏松或骨硬化中观察到的骨髓空间减少，由于骨髓环境的改变，导致肝脏和脾脏继发性髓外造血。骨稳态的改变是否也影响适应性免疫尚不清楚。因此，我们想分析骨硬化和骨质疏松对适应性免疫反应的影响，以确定骨髓中淋巴细胞的发育是否对免疫系统的发育至关重要。