Ifnlr1, or interferon lambda receptor 1, is a type II cytokine receptor. It binds to interleukins IL-28A, IL-29B, and IL-29 (type III IFNs or IFN-λs), and through the JAK-STAT signaling pathway, IFN-λs exert antiviral effects, playing a crucial role in the body's immune response [1,2]. Genetic models such as zebrafish and mice are valuable for studying its functions.

In pigs, overexpression of porcine Ifnlr1 suppresses porcine reproductive and respiratory syndrome virus (PRRSV) replication, inhibits the proliferation of porcine alveolar macrophages (PAMs), and upregulates antiviral and IFN-stimulated genes. Knockdown of Ifnlr1 expression promotes PAMs proliferation [1]. In zebrafish, knockdown of ifnlr1 leads to a decrease in hair cells and non-inflation of the swim bladder, and upregulates genes in the Jak1/STAT3 pathway, indicating its importance in the auditory system [4]. In a mouse model of TLR7-induced lupus, Ifnlr1 deficiency significantly reduces immune cell activation and associated organ damage in the skin and kidneys [3].

In conclusion, Ifnlr1 is essential for the body's antiviral immune response and has a significant impact on various biological processes. Studies using gene-knockout models in different species have revealed its role in viral infections like PRRSV, in the auditory system, and in autoimmune diseases such as lupus, providing insights into potential therapeutic strategies for related diseases.

References:

1. Qin, Ming, Chen, Wei, Li, Zhixin, Zhao, Jing, Zeng, Yongqing. . Role of IFNLR1 gene in PRRSV infection of PAM cells. In Journal of veterinary science, 22, e39. doi:10.4142/jvs.2021.22.e39. https://pubmed.ncbi.nlm.nih.gov/34056880/

2. Evans, John Grayson, Novotny, Laura A, Meissner, Eric G. 2023. Influence of Canonical and Non-Canonical IFNLR1 Isoform Expression on Interferon Lambda Signaling. In Viruses, 15, . doi:10.3390/v15030632. https://pubmed.ncbi.nlm.nih.gov/36992341/

3. Goel, Rishi R, Wang, Xinghao, O'Neil, Liam J, Carmona-Rivera, Carmelo, Kaplan, Mariana J. 2020. Interferon lambda promotes immune dysregulation and tissue inflammation in TLR7-induced lupus. In Proceedings of the National Academy of Sciences of the United States of America, 117, 5409-5419. doi:10.1073/pnas.1916897117. https://pubmed.ncbi.nlm.nih.gov/32094169/

4. Gao, Xue, Yuan, Yong-Yi, Lin, Qiong-Fen, Liu, Han-Kui, Dai, Pu. 2018. Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss. In Journal of medical genetics, 55, 298-306. doi:10.1136/jmedgenet-2017-104954. https://pubmed.ncbi.nlm.nih.gov/29453195/