Development of immunotherapy using lymphoid cells ectopicallyexpressing keratin 5
Project/Area Number |
23791266
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Dermatology
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Research Institution | Osaka University |
Principal Investigator |
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Project Period (FY) |
2011 – 2012
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Project Status |
Completed (Fiscal Year 2012)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 皮膚自己免疫疾患 / 樹状細胞 / 動物モデル / 抗原提示細胞 / B-1 細胞 / B-1細胞 / B細胞 |
Research Abstract |
Keratin 5 (K5) is a cytoskeletal tissue-specific protein expressed in the epithelial cells of skin and esophagus. Although K5 is also expressed in lymphoid organs such as thymus, ectopic K5 expression in lymphocytes has never been reported. Since K5 expression in epidermal keratinocytes is transient during epidermal differentiation, not all keratinocytes express K5. Here we demonstrate an ectopic epidermal self-protein expression in a part of B-1 B cell by fate mapping of K5-expressing cells. K5-Cre ×CAG-CAT-loxP-EGFP double transgenic (K5×GFP) mice that express enhanced green fluorescence protein (GFP) under the control of the K5 promoter were employed. Unexpectedly, B220^+GFP^+cells were found in lymph nodes (LNs), spleen, peripheral blood, and peritoneum. These cells were located in a non-follicular area of secondary lymph organs and were IgM+IgDlowCD23^-CD43^+CD19^+CD93^-, indicating that they were B-1 B cells, which are the major B cell subpopulation in the pleural and peritoneal cavities. Although GFP+B-1 cells did not express K5 in the periphery, LinCD93^+B220low-negCD19^+B^-1 B cell progenitors expressed GFP and B220^+CD93^+progenitor cells expressed K5 and MHC^-class II in bone marrow (BM), indicating that GFP^+B^-1 cells transiently expressed K5 and the progenitor cells were potential antigen-presenting cells. Interestingly, GFP+B^-1 cells in the periphery continued expressing MHC class II and had exogenous antigen-presentingcapacity comparable to non-follicular B cells and plasmacytoid dendritic cells. GFP^+B^-1 cells proliferated more rapidly in vivo and spontaneously secreted more IgM than GFPB-1 cells in vitro. These results indicate that a part of B-1 B cells transiently express K5 in BM and are potent for both natural antibody production and antigen presentation.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Toxic epidermal necrolysis complicated by sepsis, haemophagocytic syndrome, and severe liver dysfunction associated with elevated interleukin-10 production2012
Author(s)
Yamaoka T, Azukizawa H, Tanemura A, Murota H, Hirose T, Hayakawa K, Shimazu T, Wada N, Morii E, Katayama I
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Journal Title
Eur J Dermatol
Volume: 22(6)
Pages: 815-7
Related Report
Peer Reviewed
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[Journal Article] Lichen planus-type chronic graft-versus-host disease complicated by mucous membrane pemphigoid with positive anti-BP180/230 and scleroderma-related autoantibodies followed by reduced regulatory T cell frequency.2012
Author(s)
Hanafusa T, Azukizawa H, Nishioka M, Tanemura A, Murota H, Yoshida H, Sato E, Hashii Y, Ozono K, Koga H, Hashimoto T, Katayama I
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Journal Title
Eur J Dermatol.
Volume: 22(1)
Pages: 140-2
Related Report
Peer Reviewed
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[Journal Article] Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction of antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells.2011
Author(s)
Azukizawa H, Doehler A, Kanazawa N, Nayak A, Lipp M, Malissen B, Autenrieth I, Katayama I, Riemann M, Weih F, Berberich-Siebelt F, Lutz MB.
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Journal Title
Eur J Immunol.
Volume: 41(5)
Pages: 1420-34
Related Report
Peer Reviewed
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[Journal Article] Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8α+ type.2011
Author(s)
Crozat K, Tamoutounour S, Vu Manh TP, Fossum E, Luche H, Ardouin L, Guilliams M, Azukizawa H, Bogen B, Malissen B, Henri S, Dalod M
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Journal Title
J Immunol.
Volume: 187(9)
Pages: 4411-5
Related Report
Peer Reviewed
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[Journal Article] Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma.2011
Author(s)
Kitaba S, Murota H, Terao M, Azukizawa H, Terabe F, Shima Y, Fujimoto M, Tanaka T, Naka T, Kishimoto T, Katayama I
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Journal Title
Am J Pathol.
Volume: 180(1)
Pages: 107-12
Related Report
Peer Reviewed
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[Presentation] 呼吸困難と急激な体重減少を伴い、腫瘍随伴性天疱瘡が疑われた、抗デスモコリン1、2、3IgG抗体陽性の粘膜型水疱症の1例
Author(s)
中山 育徳, 中野 真由子, 山岡 俊文, 小豆澤 宏明, 種村 篤, 玉井 克人, 片山 一朗, 古賀 浩嗣, 橋本 隆, 三浦 宏之, 崎元 和子
Organizer
大阪地方会
Place of Presentation
大阪
Related Report
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