SPP 1468:  Osteoimmunology - IMMUNOBONE - A Programme to Unravel the Mutual Interactions between the Immune System and Bone

• Subject Area: Medicine
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 130243000

Osteoimmunology is an emerging field that combines immunologic and musculoskeletal research. The interactions between bone and the immune system were recognised less than ten years ago by the discovery of a protein termed Receptor Activator of NF-kB Ligand (RANKL). Since then, interest in this field has increased dramatically and novel insights into the mutual regulation of bone and the immune system have been achieved. Major fields of interest are the regulation of bone mass and architecture by the immune system in inflammatory diseases as well as the characterisation of bone marrow as an organ required for the differentiation and survival of immune cells.
The Priority Programme IMMUNOBONE is intended to develop this new field of research and to decipher key molecular, cellular and clinical mechanisms in the interplay between these two organ systems, to develop and to adopt new therapies.
As shown in clinical observations, inflammatory and autoimmune diseases induce bone damage, but the molecular processes are poorly understood. Inflammatory processes can induce bone destruction and affect bone metabolism in a similar way as tumour metastases. The mediators that are actually involved in these mechanisms will be part of the investigations of the IMMUNOBONE consortium.
Also, the Priority Programme will investigate the role of bone as a “school” of the immune cells. It is already known that the majority of immune cells develop in the bone marrow closely connected with the bone substance. There are speculations that bone tissue regulates maturation and the state of immune cells. It has been suggested that immunologic memory is maintained in the bone marrow, which protects humans against infections caused by germs. Both aspects are of essential clinical importance.
To accomplish this, IMMUNOBONE will foster and strengthen the collaboration of leading researchers in the field of immunology, bone and cartilage biology, rheumatology, orthopaedic surgery, haematology and molecular genetics and establish a long-lasting consortium for cutting edge research in the field of osteoimmunology within 26 projects.

• DFG Programme: Priority Programmes
• International Connection: Austria, France, Netherlands, Sweden, Switzerland, USA

Projects

• Analysis of early immune responses and the role of mast cells in fracture healing (Applicants Dudeck, Anne ;  Ignatius, Anita )
• Bone marrow plasma cells in autoimmune lupus modulating the function of bone metabolizing cells - osteoblasts and osteoclasts (Applicant Manz, Rudolf )
• Cell type specific action of glucocorticoids in inflammation and bone integrity of rheumatoid arthritis (Applicant Tuckermann, Jan )
• Characterization of the transcription factor Gfi1 as novel regulator of bone homeostasis (Applicant Mundlos, Stefan )
• Core Facility: Morphology - Imaging - Skeletal Characterization (Applicant Amling, Michael )
• Crosstalk between inflammation, bone destruction and new bone formation in patients with ankylosing spondylitis (Applicant Syrbe, Uta )
• Delineation of human plasma cell subsets and their bone marrow niche (Applicant Dörner, Thomas )
• Dissecting the osteoimmunological role of dickkopf-1 in arthritis and glucocorticoidinduced bone loss (Applicants Hofbauer, Lorenz C. ;  Rauner, Martina )
• Evaluation of the nuclear receptor Retinoid Acid Receptor related Receptor alpha (RORalpha) as a novel regulator of osteoclastogenesis in rheumatoid arthritis and osteoporosis (Applicant Distler, Jörg Hans Wilhelm )
• Heparan sulfate in Degenerating Joint Diseases (Applicant Vortkamp, Andrea )
• How Fra/AP-1 transcription factors control the bone niche (Applicants Bozec, Aline ;  Mielenz, Dirk )
• Immunological aspects of mesenchymal stem cell -based bone regeneration and the risk for osteomyelitis (Applicant Richter, Wiltrud )
• Impact of immunoglobulin G and Fc-gamma-receptors on osteoblast and osteoclast development and function in vitro and in vivo (Applicant Nimmerjahn, Falk )
• Impact of Mast cells on synovial inflammation and bone destruction in autoimmune-induced arthritis (Applicant Dudeck, Anne )
• Interplay between the Immune System and the Bone in the SWAP-70-/-mouse (Applicant Garbe, Annette )
• Investigating the impact of entheseal resident yd T lymphocytes on tissue remodeling in spondyloarthropathy via the IL-23 - IL-17 cytokine axis. (Applicant Prinz, Immo )
• Investigation of the role of the nuclear receptor NR4a1 during bone turnover and maintenance of the hematopoietic niche in the bone marrow (Applicant Krönke, Gerhard )
• Management and Dissemination of Priority Program SPP 1468 "Osteoimmunology - IMMUNOBONE - A Programm to Unravel Mutual lnteractions between the Immune System and Bone" (Applicant Schett, Georg )
• Mesenchymal stroma cells as organizers of immunological memory in the bone marrow (Applicants Chang, Hyun-Dong ;  Radbruch, Andreas )
• Molecular mechanisms of Th17 T cell effector function on cartilage and bone matrix destruction in rheumatoid arthritis (RA) and its modulation via osteopontin (Applicant Blaschke-Steinbrecher, Sabine )
• Osteoimmunological Interactions at the Switch from Acute to Chronic Arthritis (Applicant Kamradt, Thomas )
• Pasteurella multocida toxin as a tool to modulate bone and immune cell differentiation (Applicant Hieke-Kubatzky, Katharina )
• Relevance of osteal macrophages in bone remodeling (Applicants Amling, Michael ;  Schinke, Ph.D., Thorsten )
• Role for the bone environment in regulating immune responses (Applicant David, Ph.D., Jean-Pierre )
• The effect of adipocytokines on osteoimmunological processes (Applicant Neumann, Elena )
• The impact of ACPA on bone loss in patients with rheumatoid arthritis (Applicant Schett, Georg )
• The peripheral nervous system and focal bony erosions in arthritis (Applicants Grässel, Susanne ;  Straub, Rainer H. )
• The role of CXCR2-ligands for neutrophil mobilization from the bone marrow to peripheral sites (Applicants Gunzer, Matthias ;  Waisman, Ari )
• The role of MAPK-activated protein kinase-2 and -3 in bone homeostasis and inflammatory bone destruction (Applicant Schett, Georg )
• The role of myostatin in joint destruction in rheumatoid arthritis (Applicant Dankbar, Ph.D., Berno )
• The role of the oxidative burst in bone remodeling during chronic inflammation (Applicants Herrmann, Martin ;  Hoffmann, Markus )
• The Role of the Wnt antagonist Wif-1 in bone remodelling during arthritis (Applicant Schett, Georg )

• Spokesperson: Professor Dr. Georg Schett