Department of Genetics, University of Georgia, Athens, GA, United States.
Front Immunol. 2023 Oct 6;14:1261081. doi: 10.3389/fimmu.2023.1261081. eCollection 2023.
Thymic epithelial cells (TECs) are essential for T cell development in the thymus, yet the mechanisms governing their differentiation are not well understood. Lin28, known for its roles in embryonic development, stem cell pluripotency, and regulating cell proliferation and differentiation, is expressed in endodermal epithelial cells during embryogenesis and persists in adult epithelia, implying postnatal functions. However, the detailed expression and function of Lin28 in TECs remain unknown. In this study, we examined the expression patterns of and its target in fetal and postnatal TECs and discovered opposing expression patterns during postnatal thymic growth, which correlated with FOXN1 and MHCII expression. Specifically, showed high expression in MHCII TECs, whereas was expressed in MHCII TECs. Deletion of and specifically in TECs resulted in reduced MHCII expression and overall TEC numbers. Conversely, overexpression of increased total TEC and thymocyte numbers by promoting the proliferation of MHCII TECs. Additionally, our data strongly suggest that and expression is reliant on FOXN1 to some extent. These findings suggest a critical role for Lin28 in regulating the development and differentiation of TECs by modulating MHCII expression and TEC proliferation throughout thymic ontogeny and involution. Our study provides insights into the mechanisms underlying TEC differentiation and highlights the significance of Lin28 in orchestrating these processes.
胸腺上皮细胞（TECs）对于胸腺中 T 细胞的发育至关重要，但调控其分化的机制尚不清楚。Lin28 在胚胎发生过程中在内胚层上皮细胞中表达，并在成年上皮细胞中持续存在，暗示其具有出生后的功能。然而，Lin28 在 TECs 中的详细表达和功能仍不清楚。在本研究中，我们研究了 Lin28 及其靶基因在胎儿和出生后 TECs 中的表达模式，并发现其在出生后胸腺生长过程中的表达模式相反，与 FOXN1 和 MHCII 的表达相关。具体而言，Lin28 在 MHCII TECs 中高表达，而 则在 MHCII TECs 中表达。特异性敲除 TECs 中的 和 导致 MHCII 表达和整体 TEC 数量减少。相反，通过促进 MHCII TECs 的增殖，过表达 增加了总 TEC 和胸腺细胞数量。此外，我们的数据强烈表明，在某种程度上，Lin28 的表达依赖于 FOXN1。这些发现表明 Lin28 通过调节 MHCII 表达和 TEC 增殖在整个胸腺发生和退化过程中对 TEC 发育和分化起关键作用。本研究为 TEC 分化的机制提供了新的见解，并强调了 Lin28 在协调这些过程中的重要性。
