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Nociceptors regulate osteoimmune transcriptomic response to infection
Scientific Reports ( IF 3.8 ) Pub Date : 2023-10-16 , DOI: 10.1038/s41598-023-44648-9
Katherine V Lillis 1 , Obadah Austah 1, 2 , Ruta Grinceviciute 1 , Gustavo P Garlet 3 , Anibal Diogenes 1
Affiliation  

Osteoimmune diseases, such as apical periodontitis, are prevalent, often painful, inflammatory conditions resulting in bone loss and reduced quality of life. There is growing evidence that the nociceptive fibers densely innervating affected tissues regulate disease progression; therefore, we hypothesized that nociceptors regulate the transcriptomic profile of the periapical osteolytic lesion in a mouse model of apical periodontitis. Male control and nociceptor-ablated mice underwent pulp exposures, and after 0, 7, or 14 days, total RNA from periapical tissues was submitted for sequencing and bioinformatic analysis. Pulp exposure triggers the differential expression of hundreds of genes over the course of infection. At 14 days post pulp exposure, 422 genes, including Tnf, Il1a, and Il1b, were differentially expressed between nociceptor-ablated and control mice with greater enrichment of biological processes related to inflammation in nociceptor-ablated mice. Nociceptor ablation regulates the transcriptomic profile of periapical lesions in a mouse model of apical periodontitis, shifting the gene expression profile to a greater enrichment of inflammatory genes, suggesting nociceptors play a role in the kinetics of the immune response. This newly uncovered neuro-immune axis and its mechanisms in apical periodontitis can be an important therapeutic target for the treatment of this prevalent disease.



中文翻译:


伤害感受器调节对感染的骨免疫转录组反应



骨免疫疾病,例如根尖牙周炎,是一种普遍存在的、常常引起疼痛的炎症性疾病,会导致骨质流失和生活质量下降。越来越多的证据表明,伤害性纤维密集地支配受影响的组织,调节疾病的进展。因此,我们假设伤害感受器调节根尖周炎小鼠模型中根尖周溶骨性病变的转录组学特征。雄性对照和伤害感受器消除的小鼠接受牙髓暴露,0、7或14天后,提交根尖周组织的总RNA进行测序和生物信息分析。在感染过程中,牙髓暴露会引发数百个基因的差异表达。在牙髓暴露后 14 天,包括 Tnf、Il1a 和 Il1b 在内的 422 个基因在伤害感受器消除小鼠和对照小鼠之间存在差异表达,并且伤害感受器消除小鼠中与炎症相关的生物过程更加丰富。伤害感受器消融调节根尖周炎小鼠模型中根尖周病变的转录组学特征,将基因表达特征转变为炎症基因的更大富集,表明伤害感受器在免疫反应动力学中发挥作用。这种新发现的神经免疫轴及其在根尖周炎中的机制可能成为治疗这种流行疾病的重要治疗靶点。

更新日期:2023-10-18
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