Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Licenciatura en Ciencias Genómicas, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos 62210, México.
Cell Genom. 2024 Sep 11;4(9):100636. doi: 10.1016/j.xgen.2024.100636. Epub 2024 Aug 27.
Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.
哮喘是一种由遗传和环境因素引起的复杂疾病。研究表明，鼻病毒感染时的喘息与儿童哮喘的发展有关。已经发现了超过 150 个与哮喘相关的非编码风险变异，其中许多影响 T 细胞的基因调控，但大多数风险变异的影响仍然未知。我们假设气道上皮细胞也可以介导哮喘的遗传易感性，因为它们是抵御呼吸道病毒和过敏原的第一道防线。我们将遗传数据与不同刺激下气道上皮细胞的转录组学数据进行了整合。我们证明鼻病毒感染显著上调了儿童期发病的哮喘相关基因，尤其是在无纤毛细胞中。这种富集也在流感感染中观察到，但在严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）或细胞因子激活中没有观察到。总的来说，我们的研究结果表明，鼻病毒感染是一种环境因素，通过非纤毛气道上皮细胞与遗传风险因素相互作用，导致儿童期发病的哮喘。
