2012 Fiscal Year Final Research Report
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 |
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| Research Field |
Dermatology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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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 |
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| 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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[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
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0
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
Year and Date
00000519
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