Wang Hai-Sheng, Yang Fu-Hua, Li Yuan, Pei Fei, Kulkarni Ashok B, Chen Zhi, Zhang Lu
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education [KLOBM]), School and Hospital of Stomatology, Wuhan University Wuhan, Hubei, China.
Functional Genomics Section, National Institute of Dental and Craniofacial Research, National Institutes of Health Bethesda, MD, USA.
Am J Transl Res. 2018 Aug 15;10(8):2677-2684. eCollection 2018.
Periapical lesions are the distinct result of chronic root canal infection and could generate severe bone resorption surrounding apical regions. Despite the local cytokine and cell-mediated immune responses, periapical lesions are also characterized by its auto-restrict inflammation. However, the detailed mechanism related to its auto-restriction of immune response is still unclear. Co-inhibitory immune checkpoints are important molecules which could negatively modulate immune response especially in T cell function. In this study we detected the expressional pattern of PD-1/LAG-3 in periapical lesions. Immunohistochemical staining showed that the inflammatory response including up-regulation of TNF-α and the infiltration of T cells, was severe in granuloma and restricted in periapical cyst. PD-1 and LAG-3 both could be detected in granuloma and cyst, while scarcely observed in control group. Exhausted T cells, characterized by PD-1 or LAG-3 positive, accumulated within granuloma and reduced in cyst. Our study revealed that in periapical lesions, T cell exhaustion characterized by PD-1 or LAG-3 positive, might contribute to the auto-restriction of inflammatory response in periapical lesions.
根尖周病变是慢性根管感染的显著结果，可导致根尖区域周围严重的骨质吸收。尽管存在局部细胞因子和细胞介导的免疫反应，但根尖周病变也以其自身限制性炎症为特征。然而，与其免疫反应自身限制相关的详细机制仍不清楚。共抑制性免疫检查点是重要的分子，可对免疫反应产生负调节作用，尤其是在T细胞功能方面。在本研究中，我们检测了根尖周病变中PD-1/LAG-3的表达模式。免疫组织化学染色显示，包括肿瘤坏死因子-α上调和T细胞浸润在内的炎症反应在肉芽肿中较为严重，而在根尖周囊肿中受到限制。PD-1和LAG-3在肉芽肿和囊肿中均能检测到，而在对照组中几乎未观察到。以PD-1或LAG-3阳性为特征的耗竭T细胞在肉芽肿中积聚，而在囊肿中减少。我们的研究表明，在根尖周病变中，以PD-1或LAG-3阳性为特征的T细胞耗竭可能有助于根尖周病变炎症反应的自身限制。
