Augmentation of osteoclast formation and its function in patients with IFN-g signaling abnormality

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21189
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Orthopaedic surgery
• Research Institution: Hiroshima University
• Principal Investigator: Tsumura Miyuki 広島大学, 医歯薬保健学研究院(医), 研究員 (80646274)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: STAT1 / IFNGR1 / MSMD / 原発性免疫不全症 / 破骨細胞 / iPS細胞

Outline of Final Research Achievements

STAT1 plays an important role in host immune response against viral and intracellular pathogens by mediating IFN-α/β and IFN-γ signaling. Heterozygous loss-of-function mutations in IFNGR1 and STAT1 can be molecular cause of Mendelian Susceptibility to Mycobacterial Diseases (MSMD) in human. These pathogenic mutations exert a dominant-negative effect on IFN-γ-STAT1 signaling, leading to host susceptibility to mycobacteria. Chronic and multifocal osteomyelitis is one of the representative symptoms in patients with MSMD. The histopathology of biopsied specimen shows noncaseating granuloma with abundant number of osteoclasts. Osteoclasts, bone-resorbing multinuclear cells, are derived from myeloid/monocyte lineage. IFN-γ is known to be a strong inhibitor of osteoclastogenesis through the IFN-γ-STAT1 signaling in mice. In this study, we examined the effect of IFN-γ on the formation and function of osteoclast derived from using the patients with AD IFNGR1 or STAT1 deficiency.

Free Research Field

免疫不全