2013 Fiscal Year Final Research Report
The switching mechanisms of the phenotype of murine chronic Graft-versus-Host Disease from SLE type to SSc type.
Project/Area Number |
24700438
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Laboratory animal science
|
Research Institution | Tokyo University of Science |
Principal Investigator |
OGAWA Shuuhei 東京理科大学, 生命医科学研究所, 助教 (20385553)
|
Project Period (FY) |
2012-04-01 – 2014-03-31
|
Keywords | 疾患モデル / 全身性強皮症動物モデル / GVH病 / T細胞 / CD28 / 補助シグナル / 制御性T細胞 |
Research Abstract |
In patients receiving allogeneic hematopoietic cell transplantation (HCT), chronic graft-versus-host disease (cGVHD) resembles autoimmune diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). In this study, we investigated the function of host T cells on symptoms in cGVHD. CD28-deficient mice as hosts showed an SSc-type cGVHD phenotype; in contrast, WT hosts showed an SLE-type cGVHD phenotype. Adoptive cell transfer experiments demonstrated that defects in host CD4+CD25+ Treg, but not in conventional CD4+ T cells were responsible for phenotypic conversion. Furthermore, the defect of host Treg cells altered the cytokine pattern of donor CD4+ T cells might lead to phenotypic change of cGVHD. Thus, host's CD28 signaling, particularly the pathway that drives Treg development, and host Treg cells played a protective role of the development of SSc-type cGVHD.
|
Research Products
(7 results)
-
[Journal Article] Quantitative analysis by surface plasmon resonance of CD28 interaction with cytoplasmic adaptor molecules Grb2, Gads and p85 PI3K2014
Author(s)
Higo, K., Oda, M., Morii, H., Takahashi, J., Harada, Y., Ogawa, S., and Abe, R.
-
Journal Title
Immunol Invest.
Volume: 43
Pages: 278-291
Peer Reviewed
-
[Journal Article] CD28 signaling in primary CD4+ T cells : Identification of both tyrosine phosphorylation-dependent and independent pathway2013
Author(s)
Ogawa, S., Ito, N., Watanabe, S., Watanabe, M., Inutake, Y., Sakurai, Y., Harada, Y., Kishimoto H., and Abe, R.
-
Journal Title
Int. Immunol.
Volume: 25
Pages: 671-681
Peer Reviewed
-
[Journal Article] AP-1 transcription factor is involved in ICOS gene expression downstream of TCR/CD28 signaling and cytokine receptor signaling2012
Author(s)
Watanabe, M., Nakajima, S, Ohnuki, K., Ogawa S., Yamashita, M., Nakayama, T., Murakami Y., Tanabe, K. and Abe, R.
-
Journal Title
European Journal Immunology
Volume: 42(7)
Pages: 1850-62
Peer Reviewed
-
[Presentation] The condition of host CD4+Cd25+ regulatory T cells determines the phenotype of chronic Graft-versus-Host Disease2013
Author(s)
Akieda, Y., Nakamura, T., Wakamatsu, E., Ogawa, S., Watanabe, S., and Abe, R.
Organizer
Annual Meeting of The Japanese Society for Immunology, 2013
Place of Presentation
Makuhari Messe, Chiba
Year and Date
20131211-13
-
[Presentation] The behavior of cytokines determines the cGVHD phenotype2013
Author(s)
Nakamura, T., Akieda, Y., Ogawa, S., Watanabe, S., Wakamatsu, E., and Abe, R.
Organizer
Annual Meeting of The Japanese Society for Immunology, 2013
Place of Presentation
Makuhari Messe, Chiba
Year and Date
20131211-13
-
[Presentation] Differential requirement for CD28 cytoplasmic motifs in T cell responses2013
Author(s)
Ogawa, S., Yoshida, N., Sano, S., Ohtsuka, S., Nakamura, T., Akieda, Y., Watanabe, S., and Abe, R.
Organizer
Annual Meeting of The Japanese Society for Immunology, 2013
Place of Presentation
Makuhari Messe, Chiba
Year and Date
20131211-13
-