IL1RL1, also known as ST2 receptor, is a crucial cytokine receptor. It binds to interleukin-33 (IL-33), and this interaction is involved in multiple immune-related pathways. The IL-33/IL1RL1 signaling pathway plays a significant role in immune responses, especially in type-2, type-1, and regulatory immune responses, and is associated with various diseases such as allergic, fibrotic, infectious, and chronic inflammatory diseases [2].

In acute myeloid leukemia (AML) models, IL1RL1 is dynamically expressed on Cbfb-MYH11+ leukemia stem cells. IL-33 treatment, through binding to IL1RL1, increased the serial replating ability and expression of pro-survival proteins in vitro, and IL1RL1+ cells survived chemotherapy better in vivo [3]. Further study in the human inv(16) AML cell line ME-1 showed that IL-33/IL1RL1 axis decreased drug sensitivity, increased the expression of IL-4 and IL-6, activated p38 MAPK and NF-κB, and decreased apoptosis by phosphorylating p38 MAPK [4]. In the tumor microenvironment, IL1RL1 signaling in regulatory T (Treg) cells dampened the antitumor activity of both IL-33 and PD-1 blockade. The amphiregulin (AREG)-epidermal growth factor receptor (EGFR) axis mediated cross-talk between IL1RL1+ Treg cells and cancer-associated fibroblasts (CAFs), enabling Treg cells to promote a profibrotic and immunosuppressive functional state of CAFs [1].

In conclusion, IL1RL1 is a key cytokine receptor involved in multiple biological processes and diseases. Its role in promoting cell survival in AML and impeding antitumor immunity in the tumor microenvironment has been revealed through model-based research. These findings provide insights into potential therapeutic targets for AML and cancer immunotherapy.

References:

1. Sun, Runzi, Zhao, Hongyu, Gao, David Shihong, Chen, Kong, Lu, Binfeng. 2023. Amphiregulin couples IL1RL1+ regulatory T cells and cancer-associated fibroblasts to impede antitumor immunity. In Science advances, 9, eadd7399. doi:10.1126/sciadv.add7399. https://pubmed.ncbi.nlm.nih.gov/37611111/

2. Cayrol, Corinne, Girard, Jean-Philippe. . Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. In Immunological reviews, 281, 154-168. doi:10.1111/imr.12619. https://pubmed.ncbi.nlm.nih.gov/29247993/

3. Wang, Yiqian, Richter, Lisa, Becker, Michelle, Amador, Catalina, Hyde, R Katherine. 2019. IL1RL1 is dynamically expressed on Cbfb-MYH11+ leukemia stem cells and promotes cell survival. In Scientific reports, 9, 1729. doi:10.1038/s41598-018-38408-3. https://pubmed.ncbi.nlm.nih.gov/30742053/

4. Wang, Yiqian, Luo, Huanmin, Wei, Mengyi, Hyde, R Katherine, Gong, Qing. 2020. IL-33/IL1RL1 axis regulates cell survival through the p38 MAPK pathway in acute myeloid leukemia. In Leukemia research, 96, 106409. doi:10.1016/j.leukres.2020.106409. https://pubmed.ncbi.nlm.nih.gov/32652328/