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Clarification of peripheral tolerance mechanism involved in the onset of autoimmune skin diseases

Description: Utilizing desmoglein3 (Dsg3)-specific T cells (H1 T cells), two experimental models were established for clarification and analysis of peripheral immune tolerance mechanism. In the first model, we made mice, which lack Dsg3 only in the thymus by applying thymus transplantation into Nude mice, and then performed bone marrow transplantation to these mice from H1-tg mice. In these mice, H1 T cells matured in Dsg3 deficient thymus, and then, disappeared in Dsg3 expressing periphery. In the other model, H1 T cells existing in the periphery of H1-Dsg3-/- mice were adoptively transferred into WT mice. In these WT mice, H1 T cells disappeared after proliferation. Taking advantage of these models, we clarified that peripheral immune tolerance mechanism is initiated by antigen presentation to H1 T cells in skin-draining lymph node, and divided into proliferation phase and disappearance phase, orchestrated by some kinds of cell populations.
Amount: ¥41,470,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (A)
Start date: 2014-04-01
End date: 2017-03-31
Investigator: Masayuki Amagai
Institution: Keio University
Funded outputs count: 7
Funder award ID: 26253065
OpenAlex ID: G248090533
2019 · Kohei Fujita, Svetoslav Chakarov, et al. · Proceedings of the National Academy of Sciences · 23
2016 · Yumi Fujio, Kazuo Kojima, et al. · Journal of Dermatological Science · 27
2016 · A. Okamura, R. Nakamura, et al. · British Journal of Dermatology · 6
2015 · Takeya Adachi, Tetsuro Kobayashi, et al. · Nature Medicine · 328
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