論文 - 詳細
| RRC ID | 45396 |
|---|---|
| 著者 | Sekai M, Hamazaki Y, Minato N. |
| タイトル | Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance. |
| ジャーナル | Immunity |
| Abstract |
Medullary thymic epithelial cells (mTECs) are crucial for central T cell self-tolerance. Although progenitors of mTECs have been demonstrated in thymic organogenesis, the mechanism for postnatal mTEC maintenance remains elusive. We demonstrate that implantation of embryonic TECs expressing claudin-3 and claudin-4 (Cld3,4) in a medulla-defective thymic microenvironment restores medulla formation and suppresses multiorgan autoimmunity throughout life. A minor SSEA-1(+) fraction within the embryonic Cld3,4(hi) TECs contained self-renewable clonogenic TECs, capable of preferentially generating mature mTECs in vivo. Adult SSEA-1(+)Cld3,4(hi) TECs retained mTEC reconstitution potential, although the activity decreased. The clonogenicity of TECs also declined rapidly after birth in wild-type mice, whereas it persisted in Rag2(?/?) adult mice with defective thymopoiesis. The results suggest that unipotent mTEC-restricted stem cells that develop in the embryo have the capacity to functionally reconstitute the thymic medulla long-term, thus ensuring lifelong central T cell self-tolerance. |
| 巻・号 | 41(5) |
| ページ | 753-61 |
| 公開日 | 2014-11-20 |
| DOI | 10.1016/j.immuni.2014.10.011 |
| PII | S1074-7613(14)00387-2 |
| PMID | 25464854 |
| MeSH | Animals Antigens, Tumor-Associated, Carbohydrate / biosynthesis Cell Differentiation / immunology Cells, Cultured Claudin-3 / biosynthesis Claudin-4 / biosynthesis DNA-Binding Proteins / genetics Epithelial Cells / cytology Epithelial Cells / immunology Lewis X Antigen / biosynthesis Mice Mice, Knockout Organogenesis / immunology* Self Tolerance / immunology* Stage-Specific Embryonic Antigens / biosynthesis Stem Cells / cytology Stem Cells / immunology* T-Lymphocytes / immunology* Thymus Gland / cytology* Thymus Gland / immunology |
| IF | 22.553 |
| 引用数 | 57 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | STO(RCB0536) |