Previous pneumococcal experience establishes lung-resident IL-17A-producing CD4+ memory TRM cells that accelerate neutrophil recruitment against heterotypic pneumococci. Herein, we unravel a novel crosstalk between CD4+ TRM cells and lung epithelial cells underlying this protective immunity. Depletion of CD4+ cells in pneumococcus-experienced mice diminished CXCL5 (but not CXCL1 or CXCL2) and downstream neutrophil accumulation in the lungs. Epithelial cells from experienced lungs exhibited elevated mRNA for CXCL5 but not other epithelial products such as GM-CSF or CCL20, suggesting a skewing by CD4+ TRM cells. Genome-wide expression analyses revealed a significant remodeling of the epithelial transcriptome of infected lungs due to infection history, ~80% of which was CD4+ cell-dependent. The CD4+ TRM cell product IL-17A stabilized CXCL5 but not GM-CSF or CCL20 mRNA in cultured lung epithelial cells, implicating posttranscriptional regulation as a mechanism for altered epithelial responses. These results suggest that epithelial cells in experienced lungs are effectively different, owing to their communication with TRM cells. Our study highlights the role of tissue-resident adaptive immune cells in fine-tuning epithelial functions to hasten innate immune responses and optimize defense in experienced lungs, a concept that may apply broadly to mucosal immunology.

中文翻译：

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肺炎期间，肺 CD4+ 常驻记忆 T 细胞重塑上皮反应以加速中性粒细胞募集。

先前的肺炎球菌经验建立了肺驻留的产生 IL-17A 的 CD4+ 记忆 TRM 细胞，这些细胞加速了针对异型肺炎球菌的嗜中性粒细胞募集。在此，我们揭示了 CD4+ TRM 细胞和肺上皮细胞之间的一种新型串扰，这种串扰是这种保护性免疫的基础。肺炎球菌感染小鼠中 CD4+ 细胞的耗竭减少了肺中的 CXCL5（但不是 CXCL1 或 CXCL2）和下游中性粒细胞积聚。来自经验丰富的肺的上皮细胞表现出 CXCL5 的 mRNA 升高，但其他上皮产物（如 GM-CSF 或 CCL20）则没有，这表明 CD4+ TRM 细胞存在偏差。全基因组表达分析显示，由于感染史，受感染肺部的上皮转录组发生了显着重塑，其中约 80% 依赖于 CD4+ 细胞。CD4+ TRM 细胞产物 IL-17A 稳定了培养的肺上皮细胞中的 CXCL5 而不是 GM-CSF 或 CCL20 mRNA，表明转录后调节是改变上皮反应的机制。这些结果表明，由于与 TRM 细胞的交流，经验丰富的肺部上皮细胞实际上是不同的。我们的研究强调了组织驻留的适应性免疫细胞在微调上皮功能以加速先天免疫反应和优化有经验的肺部防御方面的作用，这一概念可能广泛应用于粘膜免疫学。由于他们与 TRM 细胞的沟通。我们的研究强调了组织驻留的适应性免疫细胞在微调上皮功能以加速先天免疫反应和优化有经验的肺部防御方面的作用，这一概念可能广泛应用于粘膜免疫学。由于他们与 TRM 细胞的沟通。我们的研究强调了组织驻留的适应性免疫细胞在微调上皮功能以加速先天免疫反应和优化有经验的肺部防御方面的作用，这一概念可能广泛应用于粘膜免疫学。