γδT细胞介导新生羔羊传染性脓疱皮炎免疫病理损伤的机制研究

Development of orf in neonatal goats is usually associated with severe inflammatory responses in the lip tissues and high mortality of the affected animals. γδT cells, which are extensively distributed in epithelial tissues, can induce the recruitment of neutrophils through IL-17 production, thereby orchestrating inflammatory responses and resulting in inflammation-mediated tissue injury. However, no studies have linked these cells with the tissue pathology during development of orf in neonatal goats. M2 macrophages and regulatory T cells are two main subsets of immunoregulatory cells; their maintenance of immune homeostasis is crucial to protect against inflammation-mediated tissue injury. However, how they regulate the inflammation of inflicted tissues during development of orf in neonatal goats is not yet clear. This project is focused on clarifying how γδT cells mediate the immunopathology of affected tissues during development of orf in neonatal goats and why neonates are more sensitive to this disease, trying to reveal the interrelationship among γδT cell-mediated tissue inflammation and immuneregulatory cell function using flow cytometry, ELISA and immunofluorescence. This project will help clarify the immunopathology of orf in neonatal goats, and can also provide novel evidence for the therapeutic strategies of this disease.

新生羔羊传染性脓疱皮炎（Orf）的发生通常伴随着唇部组织严重的炎症反应和病理损伤。γδT细胞在口唇等上皮组织广泛分布，能够通过分泌IL-17募集中性粒细胞，诱发炎症反应，造成机体的免疫病理损伤。然而，尚无研究将γδT细胞与新生羔羊Orf的组织病理损伤联系起来。M2型巨噬细胞和调节性T细胞（Treg）是重要的免疫负调细胞，由其维持的免疫稳态是使机体避免出现过强炎症反应的重要保障，而它们在Orf羔羊患部炎症反应中的具体调节机制尚不明确。本项目将利用流式细胞术、ELISA、免疫荧光染色等技术，揭示γδT细胞介导新生羔羊Orf免疫病理损伤的机制，并从Treg和M2型巨噬细胞的免疫调控功能方面进行分析，阐明免疫调节细胞在由γδT细胞所诱发的炎症反应中的重要作用，从而揭示新生羔羊作为Orf易感群体的免疫学机理。该项目将为阐明新生羔羊Orf的免疫学发病机理提供理论基础，也为Orf的治疗提供新的科学依据。

羊传染性脓疱皮炎（Orf）是由传染性脓疱病毒（Orf virus, ORFV）感染所引起的一种多发于绵羊和山羊的传染病。该病传染性强，发病率高，严重危害我国养羊业的发展，是我国农业农村部发布的绵羊和山羊的三类动物疫病。成年山羊感染ORFV后通常症状较轻，能够自愈，而新生羔羊感染后的死亡淘汰率很高，但其中的机制尚不明确。本研究以白细胞介素17（IL-17）介导的炎症反应为切入点，探究了ORFV感染引起山羊唇组织IL-17的分泌进而诱导组织免疫病理损伤的机制。研究结果表明，ORFV感染可刺激山羊唇组织γδT细胞和Th17细胞分泌IL-17，进一步引起中性粒细胞在组织局部的大量募集，引起过强的炎症反应和组织的病理损伤。另外，新生羔羊无论在健康状态还是ORFV感染状态，其IL-17和γδT细胞水平均显著高于成年羊，而其调节性T细胞水平显著低于成年羊。本研究明确了IL-17是介导新生羔羊Orf免疫病理损伤的关键因子，从炎症反应与免疫病理损伤这一全新的角度阐述了新生羔羊Orf的发病机制，揭示了新生羔羊作为ORFV易感群体的免疫学机理，研究结果可为该疾病治疗措施的制定提供新的理论依据。