Il1r2, a member of the IL-1 receptor family, is a decoy receptor that binds to IL-1 and plays a role in inhibiting the IL-1 pathway [3,5]. It is involved in modulating innate immunity and inflammation, and may participate in various biological processes [3,5]. Genetic models, such as gene knockout mouse models, can be valuable for studying its functions.

In triple-negative breast cancer, Il1r2 blockade in mouse models attenuated macrophage recruitment and TAM polarization, inhibited BTIC self-renewal and CD8+ T-cell exhaustion, reducing tumor burden and prolonging survival. Combined treatment with an Il1r2-neutralizing antibody and anti-PD-1 enhanced antitumor efficacy [1]. In clear cell renal cell carcinoma, depletion of Il1r2 in cells inhibited proliferation, migration, invasion, and arrested the cell cycle at the G1 phase, while overexpression reversed this effect, suggesting its role in tumor progression via the JAK2/STAT3 pathway [2]. In breast cancer, high Il1r2 expression was associated with poor survival, and its blockade suppressed tumorigenesis and progression by impairing USP15-dependent BMI1 stability [4]. In monocyte-related inflammation models using conditional deficient mice, Il1r2 deficiency in monocytes dysregulated their trafficking to inflamed tissues, exacerbating autoimmune neuro-inflammation [6].

In conclusion, Il1r2 plays a significant role in modulating inflammation and is involved in the progression of multiple cancers, such as triple-negative breast cancer, clear cell renal cell carcinoma, and breast cancer. The use of Il1r2 knockout or conditional knockout mouse models has provided insights into its functions in these disease conditions, highlighting its potential as a therapeutic target.

References:

1. Xia, Jie, Zhang, Lixing, Peng, Xilei, Chen, Ceshi, Liu, Suling. . IL1R2 Blockade Alleviates Immunosuppression and Potentiates Anti-PD-1 Efficacy in Triple-Negative Breast Cancer. In Cancer research, 84, 2282-2296. doi:10.1158/0008-5472.CAN-23-3429. https://pubmed.ncbi.nlm.nih.gov/38657120/

2. Liu, Yingting, Xing, Zhaoyu, Yuan, Maoling, Zhang, Jinping, Jiang, Jingting. 2022. IL1R2 promotes tumor progression via JAK2/STAT3 pathway in human clear cell renal cell carcinoma. In Pathology, research and practice, 238, 154069. doi:10.1016/j.prp.2022.154069. https://pubmed.ncbi.nlm.nih.gov/36029680/

3. Boraschi, Diana, Italiani, Paola, Weil, Sabrina, Martin, Michael U. . The family of the interleukin-1 receptors. In Immunological reviews, 281, 197-232. doi:10.1111/imr.12606. https://pubmed.ncbi.nlm.nih.gov/29248002/

4. Zhang, Lixing, Qiang, Jiankun, Yang, Xiaoli, Shao, Zhi-Ming, Liu, Suling. 2019. IL1R2 Blockade Suppresses Breast Tumorigenesis and Progression by Impairing USP15-Dependent BMI1 Stability. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 7, 1901728. doi:10.1002/advs.201901728. https://pubmed.ncbi.nlm.nih.gov/31921558/

5. Garlanda, Cecilia, Dinarello, Charles A, Mantovani, Alberto. . The interleukin-1 family: back to the future. In Immunity, 39, 1003-18. doi:10.1016/j.immuni.2013.11.010. https://pubmed.ncbi.nlm.nih.gov/24332029/

6. Cros, Adeline, Segura, Elodie. 2024. IL1R2 Acts as a Negative Regulator of Monocyte Recruitment During Inflammation. In European journal of immunology, 55, e202451468. doi:10.1002/eji.202451468. https://pubmed.ncbi.nlm.nih.gov/39610166/