Probiotic DNA regulates intestinal Th2 polarization by inducing epithelial cells to produce PD-L1

Th2 polarization is a characteristic feature of many immune diseases; its pathogenesis is still being elucidated. Probiotics have immune regulatory effects. This study is aimed at testing the impact of Lactobacillus rhamnosus (LR) DNA on regulating Th2 polarization and elucidating its underlying mechanism. In this study, ovalbumin plus alum protocol was used to establish the Th2 polarization status in the mouse intestine. Mice received LR-DNA gavage daily for five days. The expression of programmed cell death ligand-1 (PD-L1) in intestinal epithelial cells was assessed using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. The results showed that the expression of PD-L1 was detected in mouse intestinal epithelial cells, which was up regulated by LR-DNA gavage daily for 5 days. The expression of PD-L1 was also detected in T84 cells, which could be increased by exposing them to LR-DNA in culture. RNA sequencing results showed that the gene activities of Kdm5a, foxo1 and Pdl1 could be upregulated by LR-DNA in mouse intestinal epithelial cells. The epithelial cell-derived PD-L1 induced the activated Th2 cell apoptosis by interacting with programmed cell death protein-1 (PD-1). Administration of LR-DNA, but not live probiotics, alleviated experimental Th2 polarization in a food allergy mouse model. In conclusion, LR-DNA induces intestinal epithelial cells to produce PD-L1, which induces the activated Th2 cell apoptosis. Administration of LR-DNA mitigated experimental Th2 polarization in the intestine.