Zhang Hong, Zhang Hongyu, Leng Qing, Zheng Ya Juan
Department of Ophthalmology, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China.
Department of Ophthalmology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
J Inflamm Res. 2025 May 8;18:6061-6076. doi: 10.2147/JIR.S511048. eCollection 2025.
Allergic conjunctivitis (AC) is a common inflammatory condition characterized by immune dysregulation in response to environmental allergens. Despite extensive research into general allergic mechanisms, the specific immunological features of the ocular mucosal microenvironment remain poorly understood. Investigating immune-related mRNAs and LncRNAs may provide insights into the mechanisms underlying AC and potential novel targets for therapeutic intervention.
An AC model was established using female BALB/c mice sensitized with ragweed pollen. Conjunctival tissues from AC and control groups were pooled for RNA extraction, followed by Illumina sequencing. Differential gene expression was identified using DESeq2, and functional enrichment was analyzed using GO, KEGG, and GSEA. RT-qPCR validated results, while the Human Protein Atlas was used to assess protein expression.
A murine model of AC was successfully established, confirmed by progressively increasing clinical scores and significantly elevated scratching frequency. Transcriptomic analysis revealed significant differences in mRNAs and lncRNAs expression between AC and control groups. GO analysis indicated that both upregulated and downregulated genes were enriched in biological processes related to response to stimulus, immune system processes, signaling, and metabolic processes. KEGG analysis showed that upregulated genes were enriched in pathways such as steroid hormone biosynthesis, histidine metabolism, glycolysis/gluconeogenesis, and IL-17 signaling, while downregulated genes were involved in cytokine-cytokine receptor interaction and hematopoietic cell lineage. GSEA identified significant enrichment in inflammatory pathways, including MAPK, STAT1, and STAT2. Mucosal immunity-related genes such as Bpifa1, Lcn2, and Reg3g were upregulated in AC. Co-expression analysis also revealed several upregulated lncRNAs, including Stoml3-202 and Etohd2-205.
This study is the first to systematically analyze immune-related mRNAs and LncRNAs in AC, identifying mucosal immunity molecules like Bpifa1 and Reg3g. These findings underscore the unique involvement of mucosal immunity in AC and provide potential new targets for immune modulation in ocular allergy treatment.
过敏性结膜炎（AC）是一种常见的炎症性疾病，其特征是对环境过敏原产生免疫失调。尽管对一般过敏机制进行了广泛研究，但眼黏膜微环境的具体免疫特征仍知之甚少。研究免疫相关的mRNA和长链非编码RNA（LncRNA）可能有助于深入了解AC的发病机制，并为治疗干预提供潜在的新靶点。
使用豚草花粉致敏的雌性BALB/c小鼠建立AC模型。将AC组和对照组的结膜组织收集起来进行RNA提取，随后进行Illumina测序。使用DESeq2鉴定差异基因表达，并使用GO、KEGG和GSEA进行功能富集分析。通过RT-qPCR验证结果，同时使用人类蛋白质图谱评估蛋白质表达。
成功建立了AC小鼠模型，临床评分逐渐增加和抓挠频率显著升高证实了这一点。转录组分析显示AC组和对照组之间的mRNA和LncRNA表达存在显著差异。GO分析表明，上调和下调的基因均富集于与刺激反应、免疫系统过程、信号传导和代谢过程相关的生物学过程。KEGG分析表明，上调基因富集于类固醇激素生物合成、组氨酸代谢、糖酵解/糖异生和IL-17信号传导等途径，而下调基因则参与细胞因子-细胞因子受体相互作用和造血细胞谱系。GSEA确定炎症途径存在显著富集，包括MAPK、STAT1和STAT2。AC中黏膜免疫相关基因如Bpifa1、Lcn2和Reg3g上调。共表达分析还揭示了几种上调的LncRNA，包括Stoml3-202和Etohd2-205。
本研究首次系统分析了AC中免疫相关的mRNA和LncRNA，鉴定出了如Bpifa1和Reg3g等黏膜免疫分子。这些发现强调了黏膜免疫在AC中的独特作用，并为眼部过敏治疗中的免疫调节提供了潜在的新靶点。
