TCRαβ + CD8αα + intraepithelial lymphocytes (CD8αα + αβ IELs) are a specialized subset of T cells in the gut epithelium that develop from thymic agonist selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in the near absence of CD8αα + αβ IELs. BCL6 was expressed by approximately 50% of CD8αα + αβ IELs and by the majority of thymic PD1 + IELps after agonist selection. Bcl6 deficiency blocked early IELp generation in the thymus, and its expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4 + CD8 + double-positive thymocytes exhibited increased apoptosis during agonist selection and impaired IELp differentiation and maturation. Together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα + αβ IELs.

中文翻译：

---

BCL6 是 TCRαβ + CD8αα + 上皮内淋巴细胞谱系的胸腺发育所必需的

TCRαβ+CD8αα+上皮内淋巴细胞（CD8αα+αβ IEL）是肠道上皮中 T 细胞的一个特殊亚群，由胸腺激动剂选择的 IEL 前体 (IELps) 发育而来。胸腺中这种 T 细胞类型的选择和分化的分子机制在很大程度上尚不清楚。在这里，我们发现Bcl6αβ T 细胞缺陷导致 CD8αα 几乎缺失+αβ IEL。 BCL6 由大约 50% 的 CD8αα 表达+αβ IEL 和大部分胸腺 PD1+选择激动剂后的 IELps。Bcl6缺陷阻碍了胸腺中早期 IELp 的产生，并且其在 IELp 中的表达是由胸腺 TCR 信号以 ERK 依赖性方式诱导的。后果Bcl6缺陷，CD4 中 IELps 的前体+CD8+双阳性胸腺细胞在激动剂选择过程中表现出细胞凋亡增加，并且 IELp 分化和成熟受损。总之，我们的结果阐明了 BCL6 作为 CD8αα 胸腺发育过程中的关键转录因子+αβ IEL。