2010 Fiscal Year Final Research Report
The mechanisms for the deterioration of infection control in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
| Project/Area Number |
19209037
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Kyushu University |
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Principal Investigator |
NAGAFUCHI Seiho Kyushu University, 医学研究院, 教授 (00150441)
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| Co-Investigator(Kenkyū-buntansha) |
KURISAKI Hironori 九州大学, 医学研究院, 助教 (70403962)
MITSUYAMA Masao 九州大学・京都大学, 医学研究院・大学院・医学研究科, 教授 (10117260)
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| Project Period (FY) |
2007 – 2010
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| Keywords | 感染防御 / 自己免疫性多腺性内分泌不全症・カンジダ症 / 自己免疫調節遺伝子(AIRE) |
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| Research Abstract |
In order to clarify the role of AIRE gene in resist against Candida infection, we used Aire knockout mice and studied the expression of AIRE gene and protein in human peripheral immune cells. Interestingly, AIRE gene was expressed distinctively in CD4+ T cells, B cells and dendritic cells. Although AIRE gene was expressed in CD4+ T cells, AIRE protein was absent in those cells. We found that hsa-miR-anti-AIRE microRNA (tentative name) was highly expressed in CD4+ T cells, but lower in EB virus transformed B (EBV-B) cells expressing both AIRE gene and protein, indicating the microRNA may play an important role in regulating the translation of AIRE gene. We also found that both 58kDa and 45kDa AIRE related protein was expressed in dendritic cells, while EBV-B cells only expressed only 45 kDa AIRE protein, indicating multiple AIRE protein function dependent on cells expressing AIRE protein.
Experimentally, Aire knockout mice were susceptible to intravenous candida infection as worse as Rag-1 KO mice, whereas T cell deficient nu/nu mice or B cell deficient mu/mu mice could resist against candida infection, suggesting that either intact T cells or B cells are sufficient to protect against candida infection.
Whether any interactive protein or gene associate with AIRE protein remain uncertain and exact functions of AIRE gene require further study.
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Research Products
(26 results)
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[Journal Article] Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T cell tolerance.2011
Author(s)
Wada N, Nishifuji K, Yamada, Kudoh J, Shimizu N, Matsumoto M, Peltonen P, Nagafuchi S, Amagai M.
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Journal Title
J Investig Dermatol 131
Pages: 410-417
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[Presentation] The significance of B cells in the pathogenesis of type 1 diabetes and a possible role of AIRE gene.2009
Author(s)
Matsuo T, Noguchi Y, Nagao Y, Shindo M, Kogawa K, Iwakiri R, Akashi 2, Hara T, Kudoh J, Shimizu N, Kurisaki H, Katsuta H, Anzai K, Nagafuchi S.
Organizer
The 69^<th> annual meeting of American Diabetes Association Scientific Sessions
Place of Presentation
New Orleans.
Year and Date
20090605-20090609
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[Presentation] The significance of Autoimmune Regulator (AIRE) Gene, Responsible for Autoimmune Polyendocrinopathy-Candidiasis Ectodermaly Dystrophy (APECED ), in Both Central and Peripheral Immune System.2008
Author(s)
Seiho Nagafuchi, Hironori Kurisaki, Tomohito Matuso, Hiroko Hamada, Maya Iwanaga, Miki Kawano, Rimiko Koyanagi-Katsuta, Hitoshi Kat suta, Mieko Shindo, Eiko Yoshida, Kazuhiko Kogawa, Toshirou Hara, Mine Harada, Jun Kudoh, Nobuyoshi Shimizu
Organizer
The 68^<th> annual meeting of American Diabetes Association Scientific Sessions
Place of Presentation
San Francisco.
Year and Date
20080606-20080611
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