Development of immunotherapy using lymphoid cells ectopicallyexpressing keratin 5

使用异位表达角蛋白5的淋巴细胞开发免疫疗法

• 批准号: 23791266
• 负责人: AZUKIZAWA Hiroaki
• 金额: $ 2.66万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791266/
• 关键词: 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

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.

角蛋白5（K5）是一种在皮肤和食道的上皮细胞中表达的细胞骨架组织特异性蛋白。尽管K5在淋巴管等淋巴器官中也表达，但从未报道过淋巴细胞中的Ecopic K5表达。由于表皮角质形成细胞中的K5表达在表皮分化过程中是短暂的，因此并非所有角质形成细胞表达K5。在这里，我们通过表达K5的细胞的脂肪映射在B-1 B细胞的一部分中表现出异位表皮自蛋白的表达。在K5启动子控制下，K5-CRE×CAG-CAG-CAT-CAT-LOXP-EGFP双转基因（K5×GFP）小鼠在K5启动子的控制下表达增强的绿色荧光蛋白（GFP）。出乎意料的是，在淋巴结（LNS），脾脏，外周血和腹膜中发现B220^+GFP^+细胞。这些细胞位于继发性淋巴器官的非散热区域，是IgM+igdlowcd23^-cd43^+CD19^+CD93^ - ，表明它们是B-1 B细胞，它们是胸膜和腹膜和腹膜中主要B细胞的主要B细胞亚群。尽管GFP+B-1细胞在周围未表达K5，但Lincd93^+B220low-negcd19^+b^-1 B细胞祖细胞祖细胞表达GFP和B220^+CD93^+祖细胞表达的K5和MHC^-Class II在Bone Marrow（BM）中表达了bm gfp^+bm^+bm^+b.11祖细胞是潜在的抗原呈递细胞。有趣的是，外周中的GFP+B^-1细胞继续表达MHC II类，并且具有与非coll骨B细胞和浆细胞类动物树突状细胞相当的外源性抗原呈递能力。 GFP^+B^-1细胞在体内更快地增殖，并且在体外比GFPB-1细胞更快地分泌IgM。这些结果表明，B-1 B细胞的一部分在BM中瞬时表达K5，并且具有天然抗体产生和抗原呈递的潜力。

项目成果

パクリタキセル投与中にみられた顔面紅斑の２例

紫杉醇用药过程中出现面部红斑2例

• 发表时间: 2012
• 作者: 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;Hiroaki Azukizawa;小豆澤 宏明
• 通讯作者: 小豆澤 宏明

Peculiar distribution of tumorous xanthomas in an adult case of erdheim-chester disease complicated by atopic dermatitis.

成人埃德海姆-切斯特病并发特应性皮炎病例中肿瘤性黄瘤的特殊分布。

• 发表时间: 2011
• 期刊: Case Rep Dermatol.
• 作者: Murakami Y;Wataya-Kaneda M;Terao M;Azukizawa H;Murota H;Nakata Y;Katayama I
• 通讯作者: Katayama I

Erythema multiforme induced by sorafenib

索拉非尼诱发的多形红斑

• 发表时间: 2012
• 作者: 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;Hiroaki Azukizawa
• 通讯作者: Hiroaki Azukizawa

TNFα阻害薬により誘発されたと考えられる乾癬、掌蹠膿疱症の4例

TNFα抑制剂诱发银屑病和掌跖脓疱病四例

• 作者: 横見 明典;種村 篤;小豆澤 宏明;片山 一郎
• 通讯作者: 片山 一郎

薬疹におけるリンパ球刺激試験

药疹淋巴细胞刺激试验

• 作者: 横見 明典;種村 篤;小豆澤 宏明;片山 一郎;小豆澤 宏明
• 通讯作者: 小豆澤 宏明