| First Author | Teruya S | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 7021 |
| PubMed ID | 29728568 | Mgi Jnum | J:272196 |
| Mgi Id | MGI:6281294 | Doi | 10.1038/s41598-018-25302-1 |
| Citation | Teruya S, et al. (2018) Egr2-independent, Klf1-mediated induction of PD-L1 in CD4(+) T cells. Sci Rep 8(1):7021 |
| abstractText | Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4(+) T cells are unknown. Here, we revealed the potential function of Klf1 and Egr2-mediated induction of PD-L1 in CD4(+) T cells. We focused on the molecules specifically expressed in CD4(+)CD25(-)LAG3(+) regulatory T cells (LAG3(+) Tregs) highly express of PD-L1 and transcription factor Egr2. Although ectopic expression of Egr2 induced PD-L1, a deficiency of Egr2 did not affect its expression, indicating the involvement of another PD-L1 induction mechanism. Comprehensive gene expression analysis of LAG3(+) Tregs and in silico binding predictions revealed that Kruppel-like factor 1 (Klf1) is a candidate inducer of the PD-L1 gene (Cd274). Klf1 is a transcription factor that promotes beta-globin synthesis in erythroid progenitors, and its role in immunological homeostasis is unknown. Ectopic expression of Klf1 induced PD-L1 in CD4(+) T cells through activation of the PI3K-mTOR signaling pathway, independent of STATs signaling and Egr2 expression. Our findings indicate that Klf1 and Egr2 are modulators of PD-L1-mediated immune suppression in CD4(+) T cells and might provide new insights into therapeutic targets for autoimmune diseases and malignancies. |
