Panoply™ Human IL17F Knockdown Stable Cell Line

The histone demethylase JMJD2D (also known as KDM4D) specifically removes H3K9me2/3 methylation marks, thereby activating the expression of its target genes. Previous studies have shown that JMJD2D protects the intestine against dextran sulfate sodium (DSS)-induced colitis by activating the Hedgehog signaling pathway. Here, researchers investigated the role of JMJD2D in host defense against intestinal bacterial infection and the underlying mechanisms. The results demonstrated that JMJD2D expression was significantly upregulated in mouse colonic epithelial cells during Citrobacter rodentium infection. Compared with wild-type mice, JMJD2D-/- mice exhibited impaired clearance of the bacteria, more pronounced weight loss, and more severe histopathological damage in the colon. Expression of IL-17F-a cytokine that inhibits C. rodentium infection by inducing antimicrobial peptide expression-was impaired in the colonic epithelial cells of JMJD2D-/- mice. Consistently, the expression levels of β-defensin-1, β-defensin-3, and β-defensin-4 were reduced in the colonic epithelial cells of JMJD2D-/- mice. Mechanistic studies revealed that JMJD2D activates the STAT3 signaling pathway by inducing STAT3 phosphorylation; furthermore, JMJD2D interacts with STAT3 and is recruited to the IL-17F promoter region, where it cooperates with STAT3 to induce IL-17F expression by removing H3K9me3 methylation marks. These findings confirm that JMJD2D contributes to host defense against intestinal bacterial infection by upregulating IL-17F and subsequently inducing β-defensin expression.

To determine whether IL-17F promotes β-defensin expression, researchers generated an IL-17F knockdown CMT93 colorectal cancer cell line and subsequently assessed the effect of IL-17F knockdown on β-defensin expression. The expression levels of β-defensin-1, β-defensin-3, and β-defensin-4 were significantly reduced in IL-17F knockdown CMT93 cells (Figure 1A), indicating that IL-17F promotes β-defensin expression in colorectal cancer cells. Consistent with the in vivo findings, the expression of IL-17F, β-defensin-1, β-defensin-3, and β-defensin-4 was decreased in JMJD2D knockdown CMT93 cells (Figure 1B). To confirm that the promotion of β-defensin expression by JMJD2D is mediated by IL-17F, the researchers restored IL-17F expression in JMJD2D knockdown CMT93 cells. As shown in Figure 1B, ectopic expression of IL-17F in JMJD2D knockdown CMT93 cells rescued the expression of β-defensin-1, β-defensin-3, and β-defensin-4. Furthermore, they treated JMJD2D knockdown CMT93 cells with recombinant IL-17F. The results demonstrated that treatment with recombinant IL-17F also restored the expression of β-defensin-1, β-defensin-3, and β-defensin-4 in JMJD2D knockdown CMT93 cells (Figure 1C). These results indicate that JMJD2D promotes β-defensin expression by enhancing IL-17F expression.

Figure 1. JMJD2D promotes the expression of β-defensins by enhancing IL-17F expression in colon carcinoma cells. (Zhang Y, et al., 2024)