PD-L1 Inhibits T Cell-Induced Cytokines and Hyaluronan Expression via the CD40-CD40L Pathway in Orbital Fibroblasts From Patients With Thyroid Associated Ophthalmopathy

• DOI: 10.3389/fimmu.2022.849480
• Publication Date: 2022-05-10T13:07:00Z
• Authors: Zhibin Liu; Yao Liu; Mingming Liu; Qingjia Gong; Anjie Shi; Xiuhong Li; Xu Bai; Xiaoyue Guan; Bing Hao; Feila Liu; Xing Zhou; Hongfeng Yuan
• Keywords: Graves' ophthalmopathy

Thyroid associated ophthalmopathy (TAO), characterized by T cell infiltration and orbital fibroblast activation, is an organ-specific autoimmune disease which still short of effective safety therapeutic drugs. The PD-1/PD-L1 pathway has been reported hindering the progression Graves’ to some extent inhibiting activity, tumor therapy with a PD-1 inhibitor caused adverse effects similar symptoms TAO. These findings suggest that may be pathogenesis However, it remains unknown whether involved in activation. Here, we show fibroblasts from patients TAO do not express PD-L1. Based on vitro OF-T co-culture system, exogenous PD-L1 weakens cell-induced activation resulting reduced production sICAM-1, IL-6, IL-8, hyaluronan. Additionally, treatment also inhibits expression CD40 phosphorylation levels MAPK NF-κB pathways system. Knocking down siRNA or down-regulating SB203580, PD98059, SP600125, PDTC can both reduce these cytokines Our study demonstrates immune tolerance deficiency lack one causes for active inflammation patients, utilization reconstruct microenvironment potential strategy