Regulation of CD274 – Boster Bio

1. Regulation of CD274 – Boster Bio T cells, NK cells, macrophages, myeloid DCs, B cells, epithelial cells, and vascular endothelial cells all express CD274 in response to IFN- gamma. The interferon regulatory factor IRF-1 has a response element in the PD-L1 gene promoter region. On murine hepatocytes, monocytes, DCs, and tumor cells type I interferons can also upregulate PD-L1. On macrophages, CD274 (CD274 antibody) is highly expressed. Classically activated macrophages (induced by type I helper T cells or a combination of LPS and interferon-gamma) have been demonstrated to significantly upregulate PD-L1 in mice. Alternatively, IL-4-activated macrophages (alternative macrophages) upregulate CD274 marginally while upregulating PD-L2 significantly. STAT1- deficient knock-out mice have indicated that STAT1 is primarily important for the elevation of CD274 on macrophages by LPS or interferon-gamma, but not for its constitutive expression before to activation. CD274 was also shown to be expressed in a constant state on mouse Ly6Clo nonclassical monocytes. Due to translational repression by microRNA miR-513, resting human cholangiocytes express CD274 (CD274 antibody) mRNA but not the protein. MiR- 513 was downregulated in response to interferon-gamma therapy, allowing PD-L1 protein repression to be lifted. Interferon-gamma can stimulate PD-L1 protein production by blocking gene-mediated mRNA translation inhibition in this way. While Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) is a known PD- L1 inducer, EBV miRNA miR-BamH1 fragment H rightward open reading frame 1 (BHRF1) 2-5p has been demonstrated to modulate LMP1-induced PD-L1 production.