Tailoring the Immune Microenvironment of Dendritic Cells by Targeting C - type Lectin Receptor

oleh: Miao Xiong, Li Li, Yang Liu, Jun Wang, Jie-Ping Zhu

Format: Article
Diterbitkan: Wolters Kluwer Health/LWW 2017-01-01

Deskripsi

Background: The C-type lectin receptor (CLR) expressed by DCs participates in the recognition and capture of various glycosylated self-antigens and pathogens. Understanding the diversity of the CLR expressed by DCs, as well as their role in maintaining the balance between Th1-type and Th2-type cytokines would promote the understanding of the pathogenesis of many diseases including preeclampsia (PE). Methods: DCs were isolated from the placentae of healthy women who underwent normal pregnancies and infected with a CLR lentiviral (LV) vector for gene overexpression or small interfering RNA (siRNA) knockdown. DCs were cocultured with T-cells and EVCTs, and five groups were established as follows: Group 1 – DCs from healthy women who underwent normal pregnancies, Group 2 – DCs from women with preeclampsia (PE), Group 3 – DCs infected with empty LV vectors, Group 4 – DCs infected with a CLR LV vector for gene overexpression, and Group 5 – DCs infected with a CLR LV vector for siRNA knockdown. The levels of Th1- and Th2-type cytokines were measured in all groups. Results: The levels of Th1-type cytokines were significantly higher in women with PE than in those with normal pregnancies (P < 0.05). Among these five groups, the Th1/Th2 ratio of Group 5 was highest (P < 0.05). There was no difference in the Th1/Th2 ratio between Groups 1 and 3. Conclusions: There was a Th1/Th2 imbalance in women with PE displaying Th1-type immunity. CLR-overexpressing DCs showed a diminished capacity to polarize naïve T-cells into Th1 effector cells. The impaired Th1 response in DCs was rescued by CLR siRNA knockdown. In conclusion, DCs may affect the production of cytokines and the migration of T-cells through CLR-mediated signaling pathways during pregnancy.