RelB intrinsically regulates the development and function of medullary thymic epithelial cells
RelB intrinsically regulates the development and function of medullary thymic epithelial cells
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RelB本质上调节胸腺髓质上皮细胞的发育和功能
DOI：
10.1007/s11427-017-9298-3
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发表时间：
2018-09-01
影响因子：
9.1
通讯作者：
Zhu, Mingzhao
中科院分区：
文献类型：
--
作者：
Jin, Caiwei;Zhu, Mingzhao
胸腺髓质上皮细胞（mTEC）作为胸腺中的主要基质成分之一，用于选择和成熟常规T细胞和非常规T细胞。已经花费了大量的努力来了解mTEC的发展和功能是如何调节的。虽然RelB已被公认为是一个关键的转录因子mTEC的发展，潜在的机制仍然在很大程度上不清楚。在这项研究中，通过产生胸腺上皮细胞特异性RelB缺陷小鼠，我们发现上皮固有RelB是mTEC稳态增殖所必需的。从机制上讲，RelB调节参与细胞周期的基因的表达。在功能上，胸腺上皮细胞中缺乏内在RelB导致mTEC的数量急剧减少，胸腺不变的自然杀伤T（iNKT）细胞和上皮内淋巴细胞前体（IELP）的发育受损。因此，这项研究揭示了上皮固有的RelB对mTEC的发展和功能的作用。
Medullary thymic epithelial cells (mTECs) act as one of the major stromal components in the thymus for selection and maturation of both conventional T cells and non-conventional T cells. Extensive efforts have been spent to understand how mTEC development and function are regulated. Although RelB has been well accepted to be a critical transcriptional factor for mTEC development, the underlying mechanisms still remain largely unclear. In this study, by generating thymic epithelial cell specific RelB deficient mice, we found that epithelial intrinsic RelB is required for mTEC homeostatic proliferation. Mechanistically, RelB regulates the expression of genes involved in cell cycle. Functionally, lack of intrinsic RelB in thymic epithelial cells results in dramatically reduced population of mTECs and impaired development of thymic invariant natural killer T (iNKT) cells and intraepithelial lymphocyte precursors (IELPs). This study thus reveals an epithelial intrinsic role of RelB on mTEC development and function.