Il1rl2, also known as IL36R, is the gene encoding the interleukin 36 receptor. Interleukin 36 is a group of cytokines in the IL1 family with inflammatory effects. Il1rl2-related signaling pathways are involved in immune responses, tissue remodeling, and inflammation regulation, playing an important role in maintaining immune homeostasis and tissue integrity [1,3,4,5]. The development of floxed Il1rl2 mouse strain, a genetic model, can facilitate the generation of conditional knockout (CKO) mice, which is valuable for studying Il1rl2 functions [3].

In the context of disease, Il1rl2 shows diverse impacts. Inhibiting Il1rl2 gene expression or blocking its receptor signaling can reduce chronic colitis and intestinal fibrosis in mice, suggesting its role in promoting these conditions [1]. In bladder cancer, Il1rl2 is highly expressed, and its expression is an independent risk factor for overall survival, indicating its potential role in tumor progression [2]. Additionally, in a mouse model of abdominal aortic aneurysm (AAA), Il1rl2+ macrophage accumulation was observed, and IL-38, which binds to Il1rl2, can suppress AAA formation by regulating macrophages in an Il1rl2-p38 pathway-dependent manner [5].

In summary, Il1rl2 is crucial in regulating immune-related and disease-associated processes. Gene knockout (KO) or CKO mouse models of Il1rl2 have significantly contributed to understanding its role in intestinal fibrosis, bladder cancer, and AAA, providing potential therapeutic targets for these diseases.

References:

1. Scheibe, Kristina, Kersten, Christina, Schmied, Anabel, Neurath, Markus F, Neufert, Clemens. 2018. Inhibiting Interleukin 36 Receptor Signaling Reduces Fibrosis in Mice With Chronic Intestinal Inflammation. In Gastroenterology, 156, 1082-1097.e11. doi:10.1053/j.gastro.2018.11.029. https://pubmed.ncbi.nlm.nih.gov/30452921/

2. Ha, Xuemei, Li, Yue, Gao, Zihui, Sun, Lihua, Gao, Wenzhi. 2024. IL1RL2 is related to the expression and prognosis of bladder cancer. In Molecular and clinical oncology, 21, 75. doi:10.3892/mco.2024.2773. https://pubmed.ncbi.nlm.nih.gov/39170626/

3. Tongmuang, Nopprarat, Cai, Kathy Q, An, Jiahui, Novy, Mariah, Jensen, Liselotte E. 2024. Floxed Il1rl2 Locus with mCherry Reporter Element Reveals Distinct Expression Patterns of the IL-36 Receptor in Barrier Tissues. In Cells, 13, . doi:10.3390/cells13090787. https://pubmed.ncbi.nlm.nih.gov/38727323/

4. Mou, Rong, Ma, Junkai, Ju, Xuan, Feng, Ye, Lu, Xinjiang. 2024. Vasopressin drives aberrant myeloid differentiation of hematopoietic stem cells, contributing to depression in mice. In Cell stem cell, 31, 1794-1812.e10. doi:10.1016/j.stem.2024.09.018. https://pubmed.ncbi.nlm.nih.gov/39442524/

5. Kurose, Shun, Matsubara, Yutaka, Yoshino, Shinichiro, Hoshino, Tomoaki, Yoshizumi, Tomoharu. . Interleukin-38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2-p38 pathway-dependent manner. In Physiological reports, 11, e15581. doi:10.14814/phy2.15581. https://pubmed.ncbi.nlm.nih.gov/36708509/