Eosinophils accumulate adjacent to epithelial cells in the mucosa of patients with eosinophilic esophagitis (EoE), yet the bidirectional communication between these cells is not well understood. Herein, we investigated the crosstalk between human eosinophils and esophageal epithelial cells. We report that blood-derived eosinophils have prolonged survival when cocultured with epithelial cells; 96 ± 1% and 30 ± 6% viability was observed after 7 and 14 days of coculture, respectively, compared with 1 ± 0% and 0 ± 0% of monoculture. In the presence of IL-13 and epithelial cells, eosinophils had greater survival (68 ± 1%) at 14 days compared with cocultures lacking IL-13. Prolonged eosinophil viability did not require cellular contact and was observed when eosinophils were cultured in conditioned media from esophageal epithelial cells; neutralizing GM-CSF attenuated eosinophil survival. The majority of eosinophil transcripts (58%) were dysregulated in cocultured eosinophils compared with freshly isolated cells. Analysis of epithelial cell transcripts indicated that exposure to eosinophils induced differential expression of a subset of genes that were part of the EoE esophageal transcriptome. Collectively, these results uncover a network of crosstalk between eosinophils and esophageal epithelial cells involving epithelial mediated eosinophil survival and reciprocal changes in cellular transcripts, events likely to occur in EoE.

嗜酸性粒细胞在嗜酸性食管炎 (EoE) 患者的粘膜上皮细胞附近聚集，但这些细胞之间的双向交流尚不清楚。在此，我们研究了人嗜酸性粒细胞和食管上皮细胞之间的串扰。我们报告说，当与上皮细胞共培养时，血源性嗜酸性粒细胞可以延长存活时间；共培养 7 天和 14 天后分别观察到 96 ± 1% 和 30 ± 6% 的存活率，而单一培养的存活率分别为 1 ± 0% 和 0 ± 0%。在存在 IL-13 和上皮细胞的情况下，与缺乏 IL-13 的共培养物相比，嗜酸性粒细胞在 14 天时的存活率更高 (68 ± 1%)。延长的嗜酸性粒细胞活力不需要细胞接触，当嗜酸性粒细胞在食管上皮细胞的条件培养基中培养时观察到；中和 GM-CSF 减弱了嗜酸性粒细胞的存活。与新鲜分离的细胞相比，大多数嗜酸性粒细胞转录物 (58%) 在共培养的嗜酸性粒细胞中失调。对上皮细胞转录物的分析表明，暴露于嗜酸性粒细胞会诱导一部分基因的差异表达，这些基因是 EoE 食管转录组的一部分。总的来说，这些结果揭示了嗜酸性粒细胞和食管上皮细胞之间的串扰网络，涉及上皮介导的嗜酸性粒细胞存活和细胞转录物的相互变化，这些事件可能发生在 EoE 中。对上皮细胞转录物的分析表明，暴露于嗜酸性粒细胞会诱导一部分基因的差异表达，这些基因是 EoE 食管转录组的一部分。总的来说，这些结果揭示了嗜酸性粒细胞和食管上皮细胞之间的串扰网络，涉及上皮介导的嗜酸性粒细胞存活和细胞转录物的相互变化，这些事件可能发生在 EoE 中。对上皮细胞转录物的分析表明，暴露于嗜酸性粒细胞会诱导一部分基因的差异表达，这些基因是 EoE 食管转录组的一部分。总的来说，这些结果揭示了嗜酸性粒细胞和食管上皮细胞之间的串扰网络，涉及上皮介导的嗜酸性粒细胞存活和细胞转录物的相互变化，这些事件可能发生在 EoE 中。