PD-L1 在牙髓间充质干细胞免疫调节功能许可中的作用。

Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells.

机构信息

Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy.

Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy.

出版信息

Stem Cell Res Ther. 2021 Dec 4;12(1):598. doi: 10.1186/s13287-021-02664-4.

BACKGROUND

Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway.

METHODS

Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs.

RESULTS

Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status.

CONCLUSIONS

Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties.

背景

牙髓干细胞（DPSCs）免疫原性低，具有免疫调节特性，加上其已被证实的多能性，可能会增强它们在自身免疫和炎症性疾病中的应用潜力。本研究重点关注 DPSCs 通过 PD1/PD-L1 通路调节炎症微环境的能力。

方法

通过用抗 CD3 和抗 CD28 抗体激活来自健康供体和类风湿关节炎（RA）患者的 T 细胞，在体外创建炎症微环境。直接和间接共培养 DPSCs 和 PBMCs，以评估 DPSCs 中免疫调节检查点的激活和 PBMCs 中的炎症模式。

结果

我们的数据表明，炎症刺激物触发了 DPSCs 的免疫调节功能，这种功能可以通过直接和间接接触来发挥。如使用选择性 PD-L1 抑制剂所示，DPSCs 能够通过调节预激活 T 淋巴细胞中的促炎细胞因子来激活针对协调炎症过程的补偿性途径。在自体炎症状态（牙髓炎）和直接暴露于 RA 患者的预激活 T 细胞后，也观察到 PD-L1 机制的参与，这表明免疫调节/抗炎特性与其干细胞状态密切相关。