Skip to main content
Fig. 1 | Journal of Translational Medicine

Fig. 1

From: Heterogeneity of Toll-like receptor 9 signaling in B cell malignancies and its potential therapeutic application

Fig. 1

Roles of TLR9 in immune system regulation. CpG ODNs directly stimulate pDCs and B cells. The regulatory effects of TLR9 on the immune system follow a “yin-yang” principle: negative (dark segment) and positive (light segment) regulation. pDCs maturation is determined by the activation of different signaling pathways, which causes the stimulation of various cytokines and further lead to the activation of different target cells. For instance, CpG ODNs induce pDCs maturation by upregulation of the MHC and costimulatory molecules as well as secretion of cytokines and chemokines, which enhance the capability of stimulating T cells, including promoting T-cell survival and memory, enhancing CD8+ T cell cytotoxicity, and activating naive CD4+ T cells. Upon TLR9 stimulation, pDCs secrete a large amount of type I IFN, which activates NK cells, NK T cells, and monocytes. Activated NK cells further produce IFN-γ. In addition, matured pDCs subsequently promote Th1 polarization by IL-12 production. On the other hand, matured pDCs increase the expression of indoleamine 2,3-dioxygenase, resulting in the generation of inducible Tregs from naive CD4+ T cells with potent suppressor cell function via the secretion of IL-10 and TGF-β. CpG ODNs can also promote B cell proliferation and differentiation into plasma cells. Moreover, TLR9 stimulation in B cells increases the secretion of cytokines such as IL-6 and IL-10

Back to article page