Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation
Figures
Figure 1
TLR ligands and signaling pathways.…
Figure 1
TLR ligands and signaling pathways. TLRs localize to the cell surface and to…
Figure 1 TLR ligands and signaling pathways. TLRs localize to the cell surface and to intracellular vesicles such as endosomes where they respond to their exogenous and endogenous ligands as shown. The TLRs utilize adaptor proteins of the MyD88 family, including MyD88, TRIF, TIRAP, and TRAM, to initiate downstream signaling pathways that induce the activation of various transcription factors, including NF-κB, AP-1, and IRF3/7, and the production of inflammatory cytokines and type I interferons.
Figure 2
Subfamilies and the extracellular structure…
Figure 2
Subfamilies and the extracellular structure of human TLRs. (a) Human TLRs are divided…
Figure 2 Subfamilies and the extracellular structure of human TLRs. (a) Human TLRs are divided into three phylogenetic subfamilies shown with different colors. The number and cellular location of amino acid residues are shown in the middle and right columns, respectively. (b) Computational modeling of the ectodomain structure of dimerized TLR7. Blue color shows the horseshoe-shaped solenoid structure of TLR ectodomain. Arrowheads indicate undefined regions (red color).
Figure 3
The role of endosomal TLRs…
Figure 3
The role of endosomal TLRs in the development of psoriasis and the mechanism…
Figure 3 The role of endosomal TLRs in the development of psoriasis and the mechanism of action of biological drugs. Endosomal TLRs in plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs) can be triggered by self-DNA and self-RNA that forms complexes with LL37 upon its release from necrotic cells. Cytokines released by DCs further drive T cell-mediated inflammation by activating cytokines that promote leukocyte recruitment and keratinocyte activation and proliferation. Blue font: biological drugs inhibit effector cytokines in psoriatic inflammation.