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Tianyi Wang, Nabanita Biswas, PLIC-1 is an inhibitor of TLR signaling (94.7), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S171, https://doi.org/10.4049/jimmunol.178.Supp.94.7
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Abstract
Toll-like receptors (TLRs) are key innate immune receptors that recognize non-self pathogens and hence trigger host responses. We have recently identified an ubiquitin-like protein named protein linking integrin associated protein to cytoskeleton 1 (PLIC-1) that interacts with the cytoplasmic domain of TLR4. The interaction between TLR4 and PLIC-1 was verified by co-immunoprecipitation. Further studies suggest that PLIC-1 may be interacting with multiple TIR domain containing proteins. PLIC-1 decreased the production of TRIF in an overexpression system. Consequently, PLIC-1 was found to inhibit the TRIF-mediated activation of both NF-kB and IFN-b pathways in macrophages. Lastly, reduction of endogenous PLIC-1 by shRNAi delivered via retroviral infection enhanced the cellular responses to LPS or poly I:C. Together, our results have implicated PLIC-1 as a negative regulator of TLR pathway.
This work is supported by the University of Pittsburgh faculty start-up fund.