The challenge for the development of therapy for autoimmune disorder by the establishment of artificial thymic medullary organ

人工胸腺髓质器官的建立对自身免疫性疾病治疗发展的挑战

• 批准号: 23659241
• 负责人: OHIGASHI Izumi
• 金额: $ 2.41万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 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-23659241/
• 关键词: 免疫寛容; 自己免疫; 胸腺髄質上皮細胞; 自己免疫寛容性

As a step toward the establishment of an artificial thymic organ which could contribute to the treatment of autoimmune disease, the differentiation potential of thymic epithelial cells was examined. The objectives of this examination were to understand the molecular and cellular mechanisms underlying the separate development of the thymic cortical epithelial cell and thymic medullary epithelial cell lineages. We generated mice that express the recombinase Cre instead of β5t, a proteasome subunit that is abundant in thymic cortical epithelial cells and not detected in other cell types, including thymic medullary epithelial cells. By crossing β5t-Cre knock-in mice with loxP-dependent GFP reporter mice, we found that the vast majority of thymic medullary epithelial cells are differentiated fromβ5t-expressing progenitors. These results will help for the understanding of the nature of thymic microenvironment, and will give rational for the development of treatment for autoimmune disease.

作为建立有助于治疗自身免疫性疾病的人工胸腺器官的一步，检查了胸腺上皮细胞的分化潜能。本研究的目的是了解胸腺皮质上皮细胞和胸腺髓质上皮细胞谱系独立发育的分子和细胞机制。我们产生了表达重组酶Cre而不是β 5 t的小鼠，β 5 t是一种蛋白酶体亚基，在胸腺皮质上皮细胞中丰富，在其他细胞类型（包括胸腺髓质上皮细胞）中未检测到。通过将β 5 t-Cre基因敲入小鼠与loxP依赖性GFP报告基因小鼠杂交，我们发现绝大多数胸腺髓质上皮细胞是从表达β 5 t的祖细胞分化而来的。这些结果将有助于了解胸腺微环境的本质，并为自身免疫性疾病的治疗提供理论依据。

项目成果

Lymphotoxin b Receptor Regulates the Development of CC Chemokine Ligand Expressing Subset of Postnatal Medullary Thymic Epithelial Cells

淋巴毒素 b 受体调节产后胸腺髓质上皮细胞 CC 趋化因子配体表达亚群的发育

• 发表时间: 2013
• 期刊: The Journal of Immunology
• 作者: 平田雄一;小原道法;Enkhsaikhan Lkhagvasuren
• 通讯作者: Enkhsaikhan Lkhagvasuren

Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium.

• DOI: 10.1016/j.immuni.2012.01.016
• 发表时间: 2012-03-23
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Roberts NA;White AJ;Jenkinson WE;Turchinovich G;Nakamura K;Withers DR;McConnell FM;Desanti GE;Benezech C;Parnell SM;Cunningham AF;Paolino M;Penninger JM;Simon AK;Nitta T;Ohigashi I;Takahama Y;Caamano JH;Hayday AC;Lane PJ;Jenkinson EJ;Anderson G
• 通讯作者: Anderson G

Analysis of cortical and medullary bifurcation mechanisms in thymic epithelial cells using cortical thymic epithelial cell-specific β5t-Cre knock-in mice

使用皮质胸腺上皮细胞特异性 β5t-Cre 敲入小鼠分析胸腺上皮细胞的皮质和髓质分叉机制

• 作者: Inoue;D;Nagase T;OHIGASHI Izumi
• 通讯作者: OHIGASHI Izumi

胸腺皮質上皮細胞特異的β5t遺伝子座にCreをノックインしたマウスの作製

在胸腺皮质上皮细胞特异性 β5t 基因位点进行 Cre 敲入的小鼠的产生

• 作者: Izawa K;Yamanishi Y;Maehara A;Takahashi M;Isobe M;Ito S;Kaitani A;Matsukawa T;Matsuoka T;Nakahara F;Oki T;Kiyonari H;Abe T;0kumura K;Kitamura T;Kitaura J.;戸田 達史;大東いずみ
• 通讯作者: 大東いずみ

免疫不全を呈するヒトCD3eトランスジェニックマウス系統tge26におけるトランスジーン挿入部位の同定

免疫缺陷人 CD3e 转基因小鼠品系 tge26 中转基因插入位点的鉴定

• 发表时间: 2011
• 作者: Sekiya T;Kashiwagi I;Yoshida R;Fukaya T;et al.;大東いずみ;大東いずみ
• 通讯作者: 大東いずみ