整合转录组分析揭示过敏性鼻炎患者舌下过敏原免疫治疗相关的基因和细胞

文献信息

中文摘要

背景： 舌下过敏原免疫治疗（SLIT）被认为是过敏性鼻炎（AR）的有效疗法，但其疗效因治疗持续时间和个体差异而异。需要探索与SLIT持续时间和反应相关的因素。
方法： 招募了27名接受SLIT的AR患者和3名健康志愿者。分离外周血单核细胞进行RNA测序，并在可用的PBMC样本中通过定量PCR（qPCR）进一步检查关键结果。使用生物信息学工具识别和分析时间相关和反应相关基因。数据进一步与单细胞转录组整合。
结果： 我们首先识别了164个与SLIT持续时间显著相关的基因。随着治疗的进行，与免疫调节、一氧化氮和血清素转运相关的基因表达受到调控。qPCR验证进一步显示SLC6A4表达与SLIT持续时间呈显著正相关，而SH2D1B和ARG1呈正趋势。然后，我们在SLIT应答者中识别了257个上调和349个下调基因。这些基因富集于多个通路，包括干扰素信号（在应答者中上调）和粒细胞迁移（在应答者中下调）。单细胞和去卷积分析表明，自然杀伤细胞相关信号可能与SLIT疗效相关，可能与T细胞调节和嗜酸性粒细胞迁移相关的转录程序有关。
结论： 本研究揭示了与SLIT持续时间和反应相关的潜在基因和细胞。T细胞和NK细胞的调节可能在成功治疗反应中起关键作用。需要进一步研究来验证这些发现并评估其临床相关性。

英文摘要

BACKGROUND: Sublingual allergen immunotherapy (SLIT) is known as an effective therapy for allergic rhinitis (AR), although its efficacy varies across different treatment duration and individuals. The factors associated with the duration and response of SLIT need to be explored.
METHODS: Twenty-seven AR patients undergoing SLIT and three healthy volunteers were recruited. Peripheral blood mononuclear cells were isolated for RNA sequencing, and key results were further examined by quantitative PCR (qPCR) in available PBMC samples. Time-correlated and response-associated genes were identified and analyzed using bioinformatic tools. The data were further integrated with single-cell transcriptome.
RESULTS: We first identified 164 genes significantly correlated with SLIT duration. The expressions of genes associated with immunoregulation, nitric oxide and serotonin transportation were regulated as the treatment proceeded. qPCR validation further showed a significant positive correlation between SLC6A4 expression and SLIT duration, while SH2D1B and ARG1 showed positive trends. Then, we identified 257 up-regulated and 349 down-regulated genes in SLIT responders. Several pathways were enriched in these genes, including interferon signaling (up-regulated in responders) and granulocytes migration (down-regulated in responders). Single-cell and deconvolution analyses suggested that natural killer cell-associated signals may associate with SLIT efficacy, potentially in relation to T-cell-regulatory and eosinophil-migration-related transcriptional programs.
CONCLUSIONS: This study revealed potential genes and cells associated with SLIT duration and response. Regulation of T cells and NK cells may play a crucial role in the successful treatment responses. Further studies are required to validate these findings and assess their clinical relevance.