Analysis of bone remodeling using iPS cells derived from the patients with phagocyte signal transduction defects
| Project/Area Number |
25870468
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Pediatrics
Immunology
|
|---|
| 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) |
2013-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
|---|
| Keywords | 食細胞異常 / 骨髄炎 / 破骨細胞 / IFN-γ / STAT1 / IFN-γR1 / 骨リモデリング / 原発性免疫不全症 / iPS細胞 |
|---|
| Outline of Final Research Achievements |
The loss-of-function formed IFN-γR1 and STAT1 deficiency presents mendelian susceptibility to mycobacterial diseases (MSMD). Osteomyelitis is a bone infection by bacteria and other microorganism, and is one of clinical features presented in more than 80% of patients with MSMD. Osteoclasts, bone-resorbing multinuclear cells, are derived from myeloid/ monocyte lineage. IFN-γ is known to strongly suppress osteoclast formation in mice. However, the mechanism and the function of IFN-γ still remains unclear. In this study, we analyzed the formation of osteoclasts and the function of osteoclast using the mononuclear phagocytes of IFN-γR1 and STAT1 deficient patients. Our results strongly show the augmented osteoclast formation and their function in patients with MSMD through the deficiency to IFN-γ-STAT1 signal. The IFN-γ-STAT1 signal transduction system in mononuclear phagocytes may play an important role in the presentation of multiple bone lesions in MSMD patients.
|
Report
(3 results)
Research Products
(5 results)
-
[Journal Article] Simple diagnosis of STAT1 gain-of-function alleles in patients with chronic mucocutaneous candidiasis.2014
Author(s)
Mizoguchi Y, Tsumura M, Okada S, Hirata O, Minegishi S, Imai K, Hyakuna N, Muramatsu H, Kojima S, Ozaki Y, Imai T, Takeda S, Okazaki T, Ito T, Yasunaga S, Takihara Y, Bryant VL, Kong XF, Cypowyj S, Boisson-Dupuis S, Puel A, Casanova JL, Morio T, Kobayashi M.
-
Journal Title
J. Leukoc. Biol.
Volume: 95
Issue: 4
Pages: 667-76
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Naïve and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells.2013
Author(s)
Deenick EK, Avery DT, Chan A, Berglud LJ, Ives ML, Bustamante J, Boisson-Dupuis S, Tsumura M, Kobayashi M, Arkwright PD, Averbuch D, Engelhard D, Roesler J, Peake J, Wong M, Adelstein S, Choo S, Smart JM, French MA, Fulcher DA, Cook MC, Picard C, Durandy A, Klein C, Holland SM, Uzel G, Casanova JL, Ma CS, Tangye SG
-
Journal Title
Journal of Experimental Medicine
Volume: 210
Issue: 12
Pages: 2739-2753
DOI
Related Report
Peer Reviewed
-
[Journal Article] Signal transducer and activator of transcription 3 (STAT3) mutations underlying autosomal dominant hyper-IgE syndrome impair human CD8(+) T-cell memory formation and function.2013
Author(s)
Ives ML, Ma CS, Palendira U,Chan A, Bustamante J, Boisson-Dupuis S, Arkwright PD, Engelhard D, Averbuch D, Magdorf K, Roesler J, Peake J, Wong M, Adelstein S, Choo S, Smart JM, Frnch MA, Fulcher DA, Cook MC, Picard C, Durandy A, Tsumura M, Kobayashi M, Uzel G, Casanova JL, Tangye SG, Deenick EK
-
Journal Title
Journal of Allergy and Clinical Immunology
Volume: 132
Issue: 2
Pages: 400-411
DOI
Related Report
Peer Reviewed
-
-
