TLR7 Products

Description

Toll-like receptor 7 (TLR7) is a type I transmembrane protein expressed on the surface of endosomes and has a role in pathogen-associated molecular patterns (PAMPs) recognition and host defense (1-3). TLR7 is primarily expressed in the brain, placenta, spleen, stomach, and lungs (4). TLR7 recognizes microbial single stranded RNA (ssRNA), specifically guanosine and its derivatives (1-3). Human TLR7 cDNA encodes a 1049 amino acid (aa) protein with a theoretical molecular weight (MW) of 120.9 kDa (4). The TLR7 protein consists of a signal sequence, an 813 aa extracellular domain containing leucine-rich repeats (LRRs) which form a horseshoe-like shape, a 21 aa transmembrane domain, and a 189 aa cytoplasmic domain with cytosolic Toll-interleukin-1 receptor homology (TIR) domains (1,2,4). TLR7 and its fellow subfamily members, TLR8 and TLR9, possess a characteristic Z-loop between two LRRs with proteolytic Z-loop processing required for TLR activation (2). Z-loop cleavage in TLR7 allows for guanosine and uridine-rich ssRNA binding to the 1st and 2nd ligand binding site, respectively (2). The TIR domain associates with the adaptor protein myeloid differentiation primary response protein (MyD88) to initiate downstream signaling (1-3,5,6). Following activation by PAMPs, TLR7 dimerizes and bound MyD88 interacts with interleukin-1 receptor-associated kinase-4 (IRAK-4) (1,5). Together the complex recruits IRAK-1 and IRAK-2, which become phosphorylated, and interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) (1,5). TRAF6 induces the activation of mitogen-activated protein kinase (MAPK), nuclear factor-kappaB (NF-kappaB), and interferon-regulatory factor 7 (IRF7), leading to interferon production and pro-inflammatory cytokine secretion associated with immune response (1,5).

While TLRs play an important role in innate immune response, dysfunction in the TLR-MyD88 signaling cascade has also been reported in various autoimmune disorders (5,6). Elevated expression of TLR7 is associated with increased risk of system lupus erythematosus (SLE), an autoimmune disease involving B cell hyperactivity (6,7). Studies involving mouse models has also found that increased TLR7 expression predisposes mice to a lupus-like disease (7). Therapeutics targeting TLR7 have been developed to either enhance or inhibit its activity depending on the circumstance. For example, TLR7 agonists such as imiquimod, resiquimod, and 852A are used to increase TLR7 activity for treatment of cancers and to fight viral infections (7,8). On the other hand, TLR7 antagonists inhibit its activation and have been developed to combat chronic immune stimulation as seen in inflammatory and autoimmune diseases (8).

References

1. Petes C, Odoardi N, Gee K. The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome. Front Immunol. 2017;8:1075. https://doi.org/10.3389/fimmu.2017.01075

2. Maeda K, Akira S. TLR7 Structure: Cut in Z-Loop. Immunity. 2016;45(4):705-707. https://doi.org/10.1016/j.immuni.2016.10.003

3. Krieg AM, Vollmer J. Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunol Rev. 2007;220:251-269. https://doi.org/10.1111/j.1600-065X.2007.00572.x

4. Uniprot (Q9NYK1)

5. Zheng C, Chen J, Chu F, Zhu J, Jin T. Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis. Front Mol Neurosci. 2020;12:314. https://doi.org/10.3389/fnmol.2019.00314

6. Chi H, Li C, Zhao FS, et al. Anti-tumor Activity of Toll-Like Receptor 7 Agonists. Front Pharmacol. 2017;8:304. https://doi.org/10.3389/fphar.2017.00304

7. Fillatreau S, Manfroi B, Dorner T. Toll-like receptor signalling in B cells during systemic lupus erythematosus. Nat Rev Rheumatol. 2021;17(2):98-108. https://doi.org/10.1038/s41584-020-00544-4

8. Patinote C, Karroum NB, Moarbess G, et al. Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes. Eur J Med Chem. 2020;193:112238. https://doi.org/10.1016/j.ejmech.2020.112238

Bioinformatics

Entrez	170743 Mouse 317468 Rat 51284 Human
Uniprot	AAF78035 Human NM_016562 Human NP_057646 Human P58681 Mouse Q9NYK1 Human
Product By Gene ID	51284
Alternate Names	toll-like receptor 7

Research Areas for TLR7

Find related products by research area and learn more about each of the different research areas below.

Cytokine Research
Immunology
Innate Immunity
Toll-Like Receptors

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