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TLR6
TLR6 Full Name
toll-like receptor 6
TLR6 Introduction
TLR6 is part of the PRR family. It is expressed mainly on the surface of many immune system cells, such as monocytes, macrophages, and dendritic cells. Here, it senses specific molecules that are derived from microbes and in doing so initiates early defense mechanisms of the body. A characteristic of TLR6 is that it usually does not act alone, but in heterodimers with other Toll-like receptors to recognize ligands. The most classic and studied example is the heterodimerization with TLR2 to form the TLR2/TLR6 complex, which in turn is responsible for the recognition of cell wall components of Gram-positive bacteria and mycoplasma such as diacyl lipopeptides. In addition to this, TLR6 has also been shown to heterodimerize with TLR4, and to be involved in the recognition of other types of molecules.
Figure 1. Toll-like receptors and TLR-mediated signaling pathway. (Source: Zhao S, et al. 2014)
After ligand binding to the TLR6-partner receptor complex (such as TLR2), a series of complex intracellular signal transduction cascades are initiated. This process starts with the recruitment of a critical adaptor protein MyD88 to the intracellular domain of the receptors. The MyD88 activated then recruits and activates downstream signal molecules such as IRAKs and TRAF6, and ultimately leads to the activation of multiple important transcription factors such as NF-κB and AP-1, and signaling pathways such as MAPK and PI3K/AKT. The activation of these transcription factors allows them to translocate to the nucleus, where they can bind to specific DNA sequences to promote the transcription of various immune-related genes. The end result of this process is the production and release of a large number of cytokines. This includes not only pro-inflammatory factors such as TNF-α, IL-6, and IL-1β, but can also induce the expression of anti-inflammatory cytokines such as IL-10, thereby finely regulating the intensity and development of the inflammatory response.
Because of the important regulatory role of TLR6 in inflammatory responses, its dysfunctions have been associated with the pathogenesis and progression of numerous diseases. The TLR6 has been implicated in inflammatory bowel disease (IBD) as pro-inflammatory. The stimulation of TLR6 has been shown in experimental models to drive intestinal Th1 and Th17 cell responses and contribute to colonic inflammation. In a mouse model of experimental colitis, TLR6 gene knockout mice show significant amelioration of disease and a reduction in Disease Activity Index, validating the role of TLR6 as a driver of IBD pathogenesis. The TLR6 has also been shown to play a role in atherosclerosis, another inflammatory disease. It was found that TLR6 on the surface of macrophages can form a complex with TLR4 and CD36 to recognize and bind oxLDL, which are present in atherosclerotic plaques. This results in inflammatory signaling, and subsequent foam cell formation and progression of plaque.
Alternate Names for TLR6
TLR6; toll-like receptor 6; CD286;
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