When CpG Oligodeoxynucleotide enter immune cells like macrophages, plasmacytoid dendritic cells and B cells, they are recognized by toll-like receptor 9 (TLR9) which is present inside the cells' endosomes. The binding of CpG to TLR9 activates a signaling cascade that results in the activation of transcription factors like NF-κB and interferon regulatory factors. This in turn leads to increased expression of pro-inflammatory cytokines like IL-6, IL-12, tumor necrosis factor-α and type I interferons. The produced cytokines trigger both the innate and adaptive immune responses.

Allergic diseases occur due to aberrant Th2-skewed immune responses. Studies show CpG ODNs have the ability to redirect the immune response towards a Th1 phenotype by inducing IFN-γ and IL-12 production. This suppresses features of allergic asthma, rhinitis, eczema and food allergies in animal models. Recent clinical trials also found CpG ODNs reduced symptoms of seasonal allergic rhinitis in human subjects. They could provide a novel therapeutic approach for treating both IgE-mediated and non-IgE allergies.

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