UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Department of Life Sciences, Imperial College London, London, United Kingdom.
Front Immunol. 2019 Jul 19;10:1629. doi: 10.3389/fimmu.2019.01629. eCollection 2019.
Here we investigate the function of Hedgehog (Hh) signaling in thymic γδ T-cell maturation and subset differentiation. Analysis of Hh mutants showed that Hh signaling promotes γδ T-cell development in the thymus and influences γδ T-cell effector subset distribution. Hh-mediated transcription in thymic γδ cells increased γδ T-cell number, and promoted their maturation and increased the γδNKT subset, whereas inhibition of Hh-mediated transcription reduced the thymic γδ T-cell population and increased expression of many genes that are normally down-regulated during γδ T-cell maturation. These changes were also evident in spleen, where increased Hh signaling increased γδNKT cells, but reduced CD27-CD44+ and Vγ2+ populations. Systemic pharmacological Smoothened-inhibition reduced γδ T-cell and γδNKT cells in the thymus, and also reduced splenic γδ T-cell and γδNKT populations, indicating that Hh signaling also influences homeostasis of peripheral γδ T-cell populations. Taken together our data indicate that Sonic Hedgehog is an important determinant of γδ T-cell effector subset differentiation.
在这里，我们研究了 Hedgehog（Hh）信号在胸腺γδ T 细胞成熟和亚群分化中的功能。Hh 突变体的分析表明，Hh 信号促进了胸腺中γδ T 细胞的发育，并影响了γδ T 细胞效应子亚群的分布。Hh 在胸腺 γδ 细胞中的转录增加了 γδ T 细胞的数量，并促进了它们的成熟和增加了 γδNKT 亚群，而抑制 Hh 介导的转录减少了胸腺 γδ T 细胞群体，并增加了许多在 γδ T 细胞成熟过程中通常下调的基因的表达。这些变化在脾脏中也很明显，其中 Hh 信号的增加增加了 γδNKT 细胞，但减少了 CD27-CD44+和 Vγ2+群体。系统性药理学 Smoothened 抑制减少了胸腺中的 γδ T 细胞和 γδNKT 细胞，也减少了脾脏中的 γδ T 细胞和 γδNKT 群体，表明 Hh 信号也影响外周 γδ T 细胞群体的稳态。总之，我们的数据表明 Sonic Hedgehog 是 γδ T 细胞效应子亚群分化的重要决定因素。
