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
リソース情報
ヒト・動物細胞 STO(RCB0536)