Role of TLR3, 7 and 9 in SS

Role of TLR3, 7 and 9 in SS. Toll-like receptor3 (TLR3), which responds to double-strand RNA (dsRNA) of microbes, usually activates the NF-κB pathway and interferon regulatory factor (IRF) 3–7 downstream of Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF). However, TLR3 also has the ability to induce apoptosis of SGECs by activating a RIP pathway that includes the assembly of FADD and the cleavage of caspase 3. Epidermal growth factor (EGF) and EGF-mediated heme oxygenase (HO)-2 and heat shock protein (HSP)-27 are candidates for the inhibition of TLR3-mediated apoptosis. Crucial roles are also played by TLR7 and TLR9 signaling, which respond to single-strand RNA (ssRNA) and to the CpG DNA of viruses in plasmatoid dendritic cells in exocrine glands in SS, myeloid differentiation factor (MyD) 88, and its downstream pathways including the NF-κB pathway and the phosphorylation of IRF7. NF-κB and IRF7 mediate the up-regulation of inflammatory cytokines and type I interferon (IFN) including IFN-α and IFN-β. Investigations into the detailed functions of TLR7–9 signaling in epithelial cells of patients with SS are in progress.

Publication

Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome. (2018) Hideki Nakamura, et al. Int J Mol Sci. 2018 Aug;19(8):2369. Figure: F3. All organisms Mus musculus Homo sapiens Drosophila melanogaster Danio rerio

Disease mentions