Androgen Receptors in Epithelial Cells Regulate Thymopoiesis and Recent Thymic Emigrants in Male Mice
Androgen Receptors in Epithelial Cells Regulate Thymopoiesis and Recent Thymic Emigrants in Male Mice
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DOI：
10.3389/fimmu.2020.01342
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发表时间：
2020-06-29
影响因子：
7.3
通讯作者：
Tivesten, Asa
中科院分区：
文献类型：
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作者：
Wilhelmson, Anna S.;Rodriguez, Marta Lantero;Tivesten, Asa
雄激素对 T 细胞稳态具有深远影响，包括调节胸腺 T 淋巴细胞生成（胸腺生成）和最近胸腺移出物 (RTE) 的产生，即胸腺 T 淋巴细胞生成。即，源自胸腺的未成熟 T 细胞，并在次级淋巴器官中继续成熟为成熟的幼稚 T 细胞。在这里，我们研究了雄激素靶细胞对胸腺生成和脾脏和淋巴结 RTE 的影响。对一般雄激素受体敲除 (G-ARKO)、T 细胞特异性敲除 (T-ARKO) 或上皮细胞特异性敲除 (E-ARKO) 的雄性小鼠进行了检查。 G-ARKO 小鼠胸腺重量增加，胸腺 T 细胞祖细胞数量增加。这些效应不是 T 细胞固有的，因为 T-ARKO 小鼠表现出未改变的胸腺重量和胸腺生成。与胸腺上皮细胞 (TEC) 的作用一致，E-ARKO 小鼠表现出胸腺重量和胸腺 T 细胞祖细胞数量增加。此外，E-ARKO小鼠脾脏中有更多的CD4+和CD8+T细胞，并且脾脏和淋巴结中T细胞的RTE频率增加。上皮细胞中雄激素受体的消耗还与皮质（减少）和髓质（增加）TEC 相对数量的小幅变化以及胸腺髓质中 CCL25 染色的增加有关，与之前在去势小鼠中观察到的情况类似。总之，我们证明胸腺上皮是雄激素介导的胸腺生成调节的靶区室，从而产生 RTE。
Androgens have profound effects on T cell homeostasis, including regulation of thymic T lymphopoiesis (thymopoiesis) and production of recent thymic emigrants (RTEs), i. e., immature T cells that derive from the thymus and continue their maturation to mature naive T cells in secondary lymphoid organs. Here we investigated the androgen target cell for effects on thymopoiesis and RTEs in spleen and lymph nodes. Male mice with a general androgen receptor knockout (G-ARKO), T cell-specific (T-ARKO), or epithelial cell-specific (E-ARKO) knockout were examined. G-ARKO mice showed increased thymus weight and increased numbers of thymic T cell progenitors. These effects were not T cell-intrinsic, since T-ARKO mice displayed unaltered thymus weight and thymopoiesis. In line with a role for thymic epithelial cells (TECs), E-ARKO mice showed increased thymus weight and numbers of thymic T cell progenitors. Further, E-ARKO mice had more CD4(+)and CD8(+)T cells in spleen and an increased frequency of RTEs among T cells in spleen and lymph nodes. Depletion of the androgen receptor in epithelial cells was also associated with a small shift in the relative number of cortical (reduced) and medullary (increased) TECs and increased CCL25 staining in the thymic medulla, similar to previous observations in castrated mice. In conclusion, we demonstrate that the thymic epithelium is a target compartment for androgen-mediated regulation of thymopoiesis and consequently the generation of RTEs.