Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
School of Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, Australia.
Nat Immunol. 2022 Aug;23(8):1236-1245. doi: 10.1038/s41590-022-01273-4. Epub 2022 Jul 26.
Tissue-resident memory T cells (T cells) provide rapid and superior control of localized infections. While the transcription factor Runx3 is a critical regulator of CD8 T cell tissue residency, its expression is repressed in CD4 T cells. Here, we show that, as a direct consequence of this Runx3-deficiency, CD4 T cells lacked the transforming growth factor (TGF)-β-responsive transcriptional network that underpins the tissue residency of epithelial CD8 T cells. While CD4 T cell formation required Runx1, this, along with the modest expression of Runx3 in CD4 T cells, was insufficient to engage the TGF-β-driven residency program. Ectopic expression of Runx3 in CD4 T cells incited this TGF-β-transcriptional network to promote prolonged survival, decreased tissue egress, a microanatomical redistribution towards epithelial layers and enhanced effector functionality. Thus, our results reveal distinct programming of tissue residency in CD8 and CD4 T cell subsets that is attributable to divergent Runx3 activity.
组织驻留记忆 T 细胞（T 细胞）可快速有效地控制局部感染。转录因子 Runx3 是 CD8 T 细胞组织驻留的关键调节因子，但在 CD4 T 细胞中其表达受到抑制。在这里，我们发现，由于这种 Runx3 缺陷的直接结果，CD4 T 细胞缺乏支持上皮 CD8 T 细胞组织驻留的转化生长因子（TGF）-β 反应性转录网络。虽然 CD4 T 细胞的形成需要 Runx1，但这与 CD4 T 细胞中 Runx3 的适度表达一起，不足以启动 TGF-β 驱动的驻留程序。在 CD4 T 细胞中异位表达 Runx3 会激发这种 TGF-β 转录网络，促进细胞的长期存活、减少组织迁出、向上皮层的微观解剖重新分布，并增强效应功能。因此，我们的结果揭示了 CD8 和 CD4 T 细胞亚群中组织驻留的不同编程，这归因于不同的 Runx3 活性。
