Nasal cavity epithelial cells exhibit antiviral transcriptional signatures upon activation of IFN-gamma producing antigen-specific T cells

To evaluate the differential impact of IFN-gamma secretion on nasal cavity epithelial cells, we compared the transcriptional profiles of nasal cavity epithelial cells (CD45-, CD3- CD11b-, CD31-, CD326+) from wildtype and IFN-gamma knockout mice at 30 days (d30) post intranasal infection with a live attenuated influenza virus expressing the immunodominant H-2Kd CD8 T cell epitope from Sendai virus nucleoprotein (LAIV-SenNP). Nasal cavity epithelial cells were also analyzed from LAIV-SenNP immunized wildtype and IFN-gamma knockout mice 3 days after intranasal administration of Sendai virus nucleoprotein peptide (d30+3). The results indicate that nasal cavity epithelial cells express genes associated with antigen presentation and antiviral function following antigen-specific T cell activation, and these alterations in transcriptional programming depend on IFN-gamma secretion. Transcriptional profiling of 4 experimental groups (n=10 WT mice at d30, n=9 Ifng-/- mice at d30, n=10 WT mice at d30+3, and n=8 Ifng-/- mice at d30+3) collected over 2 independent replicates.

为评估干扰素-γ（IFN-gamma）分泌对鼻腔上皮细胞的差异化影响，本研究比较了野生型与干扰素-γ敲除小鼠在经鼻感染表达仙台病毒核蛋白免疫显性H-2Kd CD8 T细胞表位的减毒活流感病毒（LAIV-SenNP）后30天（d30）的鼻腔上皮细胞（CD45-、CD3- CD11b-、CD31-、CD326+）的转录谱。此外，我们还对经LAIV-SenNP免疫的野生型及干扰素-γ敲除小鼠，在经鼻给予仙台病毒核蛋白肽后3天（d30+3）的鼻腔上皮细胞进行了分析。研究结果表明，抗原特异性T细胞活化后，鼻腔上皮细胞会表达与抗原呈递及抗病毒功能相关的基因，此类转录编程的改变依赖于干扰素-γ的分泌。本研究针对4个实验组（d30时野生型小鼠n=10、d30时Ifng-/-小鼠n=9、d30+3时野生型小鼠n=10、d30+3时Ifng-/-小鼠n=8）开展转录组分析，所有样本均通过2次独立重复实验收集。