Tlr6, Toll-like receptor 6, is a type-I transmembrane receptor belonging to the Toll-like receptor family. It contains an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic Toll/IL-1 receptor-like region. TLRs play a crucial role in regulating innate and adaptive immunity. TLR6, often forming a heterodimer with TLR2, recognizes a variety of microbial ligands, activating the signaling cascade and multiple inflammatory genes [3].

The synthetic TLR2/TLR6 ligand FSL-1 promotes hematopoietic progenitor cell proliferation in mice and elevates hematopoietic cells in non-human primates after sublethal total body irradiation, suggesting its potential as a countermeasure against hematopoietic acute radiation syndrome (H-ARS) [1]. High TLR6 expression in locally advanced thoracic esophageal squamous cell carcinoma patients after esophagectomy is associated with a more favorable prognosis, and the peptidoglycan recognized by TLR6 inhibits the cell proliferation activity of esophageal squamous cell carcinoma (ESCC) lines [2]. In Helicobacter pylori infection, sustained exposure desensitizes TLR6, inducing immune tolerance, and restoration of TLR6 can reduce H. pylori colonization in the gastric mucosa, indicating TLR6 as a potential immunotherapy target [4].

In conclusion, Tlr6 is vital in the immune response, especially in recognizing microbial components and activating related signaling pathways. Research on Tlr6 using animal models has revealed its significance in diseases such as radiation-induced hematopoietic injury, esophageal cancer, and H. pylori-related gastric diseases, providing potential directions for treatment and prevention strategies.

References:

1. Brickey, W June, Caudell, David L, Macintyre, Andrew N, Cline, J Mark, Ting, Jenny P Y. 2023. The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2122178120. doi:10.1073/pnas.2122178120. https://pubmed.ncbi.nlm.nih.gov/38051771/

2. Sato, Yusuke, Wakita, Akiyuki, Maeda, Eri, Nomura, Kyoko, Minamiya, Yoshihiro. 2023. High TLR6 Expression Status Predicts a More Favorable Prognosis after Esophagectomy for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma. In Current oncology (Toronto, Ont.), 30, 4724-4735. doi:10.3390/curroncol30050356. https://pubmed.ncbi.nlm.nih.gov/37232814/

3. Noreen, Mamoona, Arshad, Muhammad. . Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility. In Immunologic research, 62, 234-52. doi:10.1007/s12026-015-8640-6. https://pubmed.ncbi.nlm.nih.gov/25784622/

4. Zhang, Xiulin, He, Yang, Zhang, Xiaolu, Chen, Zhenwen, Li, Changlong. 2024. Sustained exposure to Helicobacter pylori induces immune tolerance by desensitizing TLR6. In Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 27, 324-342. doi:10.1007/s10120-023-01461-7. https://pubmed.ncbi.nlm.nih.gov/38310631/