Role for the bone environment in regulating immune responses

• Applicant: Dr. Jean-Pierre David, Ph.D. (†)
• Subject Area: Rheumatology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 168985739

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.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1468: Osteoimmunology - IMMUNOBONE - A Programme to Unravel the Mutual Interactions between the Immune System and Bone
• Participating Person: Professor Dr. Dirk Mielenz