TLR9 Gene Editing    

Toll-like receptors (TLRs) play important roles in promoting inflammatory responses of myeloid cells in reaction to tissue stress and injury. The TLR family consists of more than 10 members in humans. TLR9 is one of the important members in this family. Ligand binding to TLR9 activates several different signaling factors, such as nuclear factor-κB (NF-κB), which is eventually characterized by increased production of inflammatory mediators. Recent studies have shown that high expression of TLR9 occurred not only in immune cells, but also in various cancer cells including brain, ovarian, breast, gastric, lung and prostate cancer cells. The role of TLR9 expressed by tumor cells in the evasion of immune surveillance was demonstrated in animal experiments, indicating that TLR9 stimulation may lead to tumor progression and inflammation and cell survival increasing.

TLR9, Cell Stress and Invasion

With regard to cell stress, experiments performed in mice showed that chronic physical stress augments TLR9 expression in macrophages, resulting in an increased production of the IL-1b, IL-10, and IL-17 cytokines in plasma. Compared with TLR9 knockout mice, TLR9 induces enhanced corticosterone (stress hormone) levels. In the same system, TLR9 induces the expression of TNF, IL-4, IL-6, and MCP-1 in splenocytic lymphocytes stimulated with concanavalin A. Therefore, chronic stress could be associated with immunosuppression, imbalance of cytokine production, and cancer development in a TLR9-mediated way. In addition, Kirillov et al. showed that a prolonged stimulation to normal human fibroblasts (NHF) with TGF-b induces TLR9 expression. Furthermore, the authors found that a long CpG stimulus to NHF-induced higher matrix metalloproteinase-14 (MMP14) expression levels and an increased capacity of invasion with respect to nonstimulated NHFs. Interestingly, CpG-stimulated NHFs had a higher survival capacity under hypoxic conditions. TLR9 expression is induced by hypoxia in D54MG and U373MG glioblastoma cell lines, and this event was associated with an increased invasive capacity. In addition, treatment with a TLR9 siRNA diminishes the invasive capacity of D54MG and U373MG cells, as well as the expression of MMP2 and MMP9.

TLR9 in Cancer

TLR9 is expressed in various cancer cell lines and different human tumors. So far, the association between TLR9 and clinicopathological parameters of cancer patients has not been widely evaluated. Tanaka et al. demonstrated that cell surface stimulation of TLR9 promotes cell proliferation and survival in human hepatocellular carcinoma. TLR9 expression has been shown to be significantly higher in high grade gliomas compared to low-grade gliomas. In breast cancer, studies show that the mRNA and protein levels of TLR9 significantly increased in recurrent breast carcinomas cells. It has been reported that TLR9 activation has distinct effects on the inflammatory, epithelial, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. In addition, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) by inducing regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Moreover, esophageal carcinomas exhibited TLR9 expression that was positively associated with tumor size, location and TNM stage (P<0.05). In lung cancers, TLR9 was found to express in a selection of human lung cancer tissues and various lung tumor cell lines. These findings indicate that high TLR9 expression and TLR9 signaling promote tumor growth, survival and immune evasion.

TLR9 Gene Editing Services

CRISPR/Cas9 Platform^CB, one of the leading biotechnological companies specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene-editing services to a wide range of genomics researchers. Based on our platform, we can help you effectively TLR9 gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• TLR9 Gene Knockout: We offer TLR9 gene knockout cell line and knockout animal model generation service with high quality. Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, but we can use other cell lines according to your requirements. Our one-stop KO animal model generation service covers from sgRNA design and construction, pronuclear microinjection to Founders genotyping and breeding.
• TLR9 Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop TLR9 knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of TLR9 knock-in cell line generation projects, including stem cells, tumor cells and even difficult-to-handle cells. We also have extensive experience in incorporating CRISPR/Cas9 technology into animal models, which have been fully recognized by our clients.

If you have any questions, please feel free to contact us.

Related Products at CRISPR/Cas9 Platform^CB

CATALOG NO.	PRODUCT NAME	PRODUCT TYPE	INQUIRY
CCKM0882	B6J-Tlr9em1Cd	Knockout Mouse	Inquiry
CDKM-0640	B6J-Tlr9em1Cflox	Knockout Mouse	Inquiry