Reference - Detail
| RRC ID | 45396 |
|---|---|
| Author | Sekai M, Hamazaki Y, Minato N. |
| Title | Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance. |
| Journal | 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. |
| Volume | 41(5) |
| Pages | 753-61 |
| Published | 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 |
| Times Cited | 57 |
| WOS Category | IMMUNOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 16 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | STO(RCB0536) |