Tlr7-KO Mouse

Tlr7, a Toll-like receptor, is a key pattern recognition receptor in the innate immune system. It recognizes pathogen-derived single-stranded RNA (ssRNA), initiating antiviral immunity and triggering the release of pro-inflammatory cytokines or type-I interferons, which is crucial for immunoregulation [1,3]. It operates via the MyD88-dependent signaling pathway [1].

In lupus, hyperactive Tlr7 signaling is a major driver. In TLR9-deficient MRL/lpr mice (a lupus-prone model), B cell-specific Tlr7 deficiency greatly improved disease, suggesting B cell-intrinsic Tlr7 expression is important for severe lupus development. This indicates a cis-regulatory interaction between protective TLR9 and pathogenic Tlr7 within the B cell compartment [4]. In rosacea, TLR7 promotes skin inflammation by activating the NFκB-mTORC1 axis. Silencing TLR7 in LL37-induced rosacea-like mouse models prevented the development of skin inflammation [2]. In pustular psoriasis, the TLR7-MyD88-DC-CXCL16 axis activates neutrophils to elicit an inflammatory response. In imiquimod-induced psoriasis-like skin lesions in mice, TLR7 influenced DC release of CXCL16 and neutrophil pro-inflammatory effects by interfering with the MyD88 signaling pathway [5].

In conclusion, Tlr7 is essential for antiviral immunity and immunoregulation. Its study using gene-knockout (KO) or conditional-knockout (CKO) mouse models has revealed its significance in autoimmune diseases such as lupus, rosacea, and pustular psoriasis. These models help in understanding the underlying molecular mechanisms, providing potential therapeutic targets for these diseases.

References:

1. Diebold, Sandra S, Kaisho, Tsuneyasu, Hemmi, Hiroaki, Akira, Shizuo, Reis e Sousa, Caetano. 2004. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. In Science (New York, N.Y.), 303, 1529-31. doi:. https://pubmed.ncbi.nlm.nih.gov/14976261/

2. Huang, Yaqun, Liu, Da, Chen, Mengting, Liu, Fangfen, Xiao, Wenqin. 2023. TLR7 promotes skin inflammation via activating NFκB-mTORC1 axis in rosacea. In PeerJ, 11, e15976. doi:10.7717/peerj.15976. https://pubmed.ncbi.nlm.nih.gov/37780385/

3. Zheng, Haoyang, Wu, Peiyang, Bonnet, Pierre-Antoine. 2023. Recent Advances on Small-Molecule Antagonists Targeting TLR7. In Molecules (Basel, Switzerland), 28, . doi:10.3390/molecules28020634. https://pubmed.ncbi.nlm.nih.gov/36677692/

4. Cosgrove, Haylee A, Gingras, Sebastien, Kim, Minjung, Tilstra, Jeremy S, Shlomchik, Mark J. 2023. B cell-intrinsic TLR7 expression drives severe lupus in TLR9-deficient mice. In JCI insight, 8, . doi:10.1172/jci.insight.172219. https://pubmed.ncbi.nlm.nih.gov/37606042/

5. Lu, Jiajing, Zhong, Xiaoyuan, Guo, Chunyuan, Zhou, Jing, Shi, Yuling. 2023. TLR7-MyD88-DC-CXCL16 axis results neutrophil activation to elicit inflammatory response in pustular psoriasis. In Cell death & disease, 14, 315. doi:10.1038/s41419-023-05815-y. https://pubmed.ncbi.nlm.nih.gov/37160878/