Identification of CD56 dim subpopulation marked with high expression of GZMB/PRF1/PI-9 in CD56 + interferon-α-induced dendritic cells

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2021-05, Vol.26 (5), p.313-327
• Main Authors: Watanabe, Asuka, Togi, Misa, Koya, Terutsugu, Taniguchi, Makoto, Sakamoto, Takuya, Iwabuchi, Kuniyoshi, Kato, Jr, Tomohisa, Shimodaira, Shigetaka
• Format: Article
• Language: English
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12844

As the sentinels of innate and adaptive immune system, dendritic cells (DCs) have been considered to hold a great promise for medical application. Among the diverse types of DCs, monocyte-derived DCs (mo-DCs) generated in vitro have been most commonly employed. We have been improving the culture protocol and devised a protocol to produce mature interferon-α-induced DCs (IFN-DCs), hereinafter called (mat)IFN-DCs. While exploring the relationship between the expression of CD56 and the cytotoxic activity of (mat)IFN-DCs, we unexpectedly found that sorting of (mat)IFN-DCs with CD56 antibody-coated microbeads (MB) resulted in fractionating cells with tumoricidal activity into the flow-through (FT) but not MB-bound fraction. We uncovered that the FT fraction contains cells expressing low but substantial level of CD56. Moreover, those cells express granzyme B (GrB), perforin (PFN), and serpin B9 at high levels. By employing a specific inhibitor of PFN, we confirmed that direct tumoricidal activity relies on the GrB/PFN pathway. We designated subpopulation in FT fraction as CD56 and that in CD56 positively sorted fraction as CD56 , respectively. This is the first time, to our knowledge, to identify subpopulations of CD56-positive IFN-DCs with distinct tumoricidal activity which is ascribed to high expression of the components of GrB/PFN pathway.