期刊
IMMUNOLOGICAL REVIEWS
卷 227, 期 -, 页码 32-43出版社
WILEY
DOI: 10.1111/j.1600-065X.2008.00729.x
关键词
TLR7; TLR9; autoimmune disease; trafficking; UNC93B1; PRAT4A
类别
Toll-like receptors (TLRs) play an important role in innate immune responses against bacteria and viruses. TLRs localize either on the cell surface or in intracellular vesicular compartments. The cell-surface TLRs, including TLR1, TLR2, TLR4, and TLR6, recognize microbial membrane lipids, whereas TLR3, TLR7, TLR8, and TLR9 recognize pathogen-derived nucleotides in intracellular compartments. TLR7 and TLR9 respond to host-derived nucleotides as well, and they have been implicated in a variety of autoimmune diseases. Safety mechanisms are required to avoid detrimental autoimmune responses. TLR7 and TLR9 are sequestered in the endoplasmic reticulum (ER) in a resting state and traffic to endolysosomes upon ligand-induced stimulation. Sequestration in the ER is a mechanism controlling TLR7/9 responses. A chaperone, gp96, in the ER is reported to regulate TLR7/9 maturation. gp96 is associated with TLR9 and is required for ligand-induced activation of TLR7/9. Two molecules in the ER are reported to regulate TLR7/9 trafficking to endolysosomes. PRAT4A (a protein associated with TLR4 A) is associated with TLR9 and is required for ligand-induced trafficking of TLR9 to endolysosomes. UNC93B1 is specifically associated with TLR3, TLR7, TLR9, and TLR13 and regulates ligand-induced trafficking of TLR7 and TLR9 from the ER to endolysosomes. These molecules are potential therapeutic targets for controlling dysregulated TLR7/9 responses in autoimmune diseases.
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