2013 Fiscal Year Final Research Report
Clarification of the molecular and cellular mechanisms of central and peripheral tolerance to pemphigus autoantigen
| Project/Area Number |
21229014
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Keisuke 慶應義塾大学, 医学部, 講師 (40286521)
KUBO Akiharu 慶應義塾大学, 医学部, 講師 (70335256)
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| Project Period (FY) |
2009-05-11 – 2014-03-31
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| Keywords | 皮膚免疫学 / 免疫寛容 / 自己免疫 / モデルマウス / 樹状細胞 / 天疱瘡 / Interface Dermatitis / 乾癬 |
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| Research Abstract |
The purpose of this study is to clarify the pathogenic roles of T cells specific for desmoglein 3 (Dsg3), the autoimmune target antigen in pemphigus vulgaris, and the mechanisms of tolerance to Dsg3 in vivo. Dsg3-specific T cells were able to induce not only pemphigus vulgaris, but also unexpectedly interface dermatitis and psoriasis-like skin lesions. This model provides an important tool to dissect the pathophysiological mechanisms for interface dermatitis as experimental autoimmune dermatitis (EAD). While Dsg3-specific T cells are usually deleted in the thymus (central tolerance), it was demonstrated that these T cells could be deleted solely in the periphery (peripheral tolerance) when thymic epithelial cells did not express Dsg3. Further dissection of the mechanisms for peripheral tolerance will lead us to develop a novel therapeutic strategy for antigen-specific immune suppression.
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[Journal Article] Autoimmune reactivity against precursor form of desmoglein 1 in healthy Tunisians in the area of endemic pemphigus foliaceus2013
Author(s)
Toumi A, Saleh MA, Yamagami J, Abida O, Kallel M, Masmoudi A, Makni S, Turki H, Hachiya T, Kuroda K, Stanley JR, Masmoudi H, Amagai M
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Journal Title
J Dermatol Sci
Volume: 70(1)
Pages: 19-25
DOI
Peer Reviewed
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[Journal Article] Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin2012
Author(s)
Nagao K, Kobayashi T, Moro K, Ohyama M, Adachi T, Kitashima DY, Ueha S, Horiuchi K, Tanizaki H, Kabashima K, Kubo A, Cho YH, Clausen BE, Matsushima K, Suematsu M, Furtado GC, Lira SA, Farber JM, Udey MC, Amagai M
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Journal Title
Nat Immunol
Volume: 13(8)
Pages: 744-752
DOI
Peer Reviewed
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[Journal Article] Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface2012
Author(s)
Di Zenzo G, Di Lullo G, Corti D, Calabresi V, Sinistro A, Vanzetta F, Didona B, Cianchini G, Hertl M, Eming R, Amagai M, Ohyama B, Hashimoto T, Sloostra J, Sallusto F, Zambruno G, Lanzavecchia A
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Journal Title
J Clin Invest
Volume: 122(10)
Pages: 3781-3790
DOI
Peer Reviewed
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[Journal Article] Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-cell tolerance2011
Author(s)
Wada N, Nishifuji K, Yamada T, Kudoh J, Shimizu N, Matsumoto M, Peltonen L, Nagafuchi S, Amagai M
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Journal Title
J Invest Dermatol
Volume: 131(2)
Pages: 410-417
DOI
Peer Reviewed
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[Journal Article] Desmoglein 3-specific CD4+ T cells induce pemphigus vulgaris and interface dermatitis in mice2011
Author(s)
Takahashi H, Kouno M, Nagao K, Wada N, Hata T, Nishimoto S, Iwakura Y, Yoshimura A, Yamada T, Kuwana M, Fujii H, Koyasu S, Amagai M
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Journal Title
J Clin Invest
Volume: 121(9)
Pages: 3677-3688
DOI
Peer Reviewed
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