TLR3 Gene

The TLR3 receptor protein, encoded by the TLR3 gene, belongs to the Toll-like receptor (TLR) family, which plays a fundamental role in recognizing pathogens and activating innate immunity. TLRs are highly conserved from Drosophila to humans and show structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) expressed on infectious agents and mediate the production of cytokines necessary for the development of effective immunity.

Toll-like receptors (TLRs) are single transmembrane cell surface receptors that play a key role in the innate immune system. TLRs usually exist as homodimers and are found on immune cells, macrophages, B lymphocytes and mast cells. They control the host's immune response against pathogens by recognizing microorganism-specific molecular patterns. TLR3 is a nucleotide-sensitive receptor that is activated by double-stranded RNA, a sign of viral infection. It acts via the TRIF/TICAM1 adaptor and leads to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and inflammatory response.

Remarkably, activation of TLR3 in the skin epithelium is essential for the normal immune response after injury. TLR3 recognizes viral double-stranded RNA (dsRNA) as well as dsRNA derived from damaged cells, leading to the expression of cytokines by keratinocytes, including IFN-β, interleukins 8, 18, 36gamma (IL-8, IL-18, IL-36γ) and tumor necrosis factor alpha (TNF-α) (Köllisch G et al. 2005; Lebre MC et al. 2003; Liu S et al. 2019) and chemokines, such as the C-C motif chemokine ligands 20 and 27 (CCL20 and CCL27). Exposure to dsRNA also leads to upregulation of the expression of receptors that recognize dsRNA, such as TLR3

Diseases associated with TLR3 include:

• Immunodeficiency 83, susceptibility to viral infections.

1. Borkowski AW et al.(2014) UVB radiation illuminates the role of TLR3 in the epidermis. J Invest Dermatol 134:2315-2320.
2. Karimi-Googheri M et al.(2014) TLR3 plays significant roles against hepatitis B virus. Mol Biol Rep 41:3279-3286.
3. Köllisch G et al. (2005) Various members of the Toll-like receptor family contribute to the innate immune response of human epidermal keratinocytes. Immunology 114:531-541.
4. Lebre MC et al. (2003) Double-stranded RNA-exposed human keratinocytes promote Th1 responses by inducing a type-1 polarized phenotype in dendritic cells: Role of keratinocyte-derived tumor necrosis factor alpha, type I interferons, and interleukin-18. J Investig Derm 120:990-997.
5. Liu Y et al.(2014) TLR2 and TLR4 in autoimmune diseases: a comprehensive review. Clin Rev Allergy Immunol 47:136-147. Matsumoto M et al.(2011) Antiviral responses induced by the TLR3 pathway. Rev Med Virol 21:67-77.
6. Perales-Linares R et al;(2013) Toll-like receptor 3 in viral pathogenesis: friend or foe? Immunology 140:153-167. Sepehri Z et al.(2015) TLR3 and its roles in the pathogenesis of type 2 diabetes. Cell Mol Biol (Noisy-le-grand) 61:46-50.
7. Wang BG et al.(2015) TLR3 gene polymorphisms in cancer: a systematic reviewand meta-analysis. Chin J Cancer 34:272-284