Il7r-KO Mouse

Il7r, encoding the interleukin-7 receptor α chain, is a crucial component of the IL-7 receptor complex. The IL-7/IL7R signaling pathway is essential for the development, survival, and homeostasis of lymphoid cells, including T-cells, B-cells, and innate lymphoid cells. It functions through major signal transduction pathways such as JAK1, JAK3 to STAT5, as well as non-canonical STAT3, STAT1, PI3K/AKT and MEK/ERK pathways [3].

Loss-of-function mutations in Lrp10 in mice lead to enhanced T-cell homeostatic expansion via IL7R signaling, indicating Lrp10 as a negative regulator of CD8 T-cell homeostasis [2]. In adult acute myeloid leukemia patients with t(8;21), low IL7R expression at diagnosis predicted relapse, potentially due to differences in T-cell amount, status, and function [1]. Mutant IL7R in transgenic zebrafish can collaborate with Myc to induce early-onset T-cell acute lymphoblastic leukemia, highlighting its oncogenic potential [4]. In acute myeloid leukemia patients, IL7R mutations are associated with inferior prognosis, including higher non-relapse mortality, shorter overall survival, and event-free survival [5].

In summary, Il7r is essential for lymphoid cell development and homeostasis. Mouse models and other in vivo studies have revealed its significant roles in cancer development and prognosis, especially in leukemia. Understanding Il7r function provides insights into disease mechanisms and may offer potential therapeutic targets for related diseases.

References:

1. Xu, Nan, Sun, Kai, Wang, Ya-Zhe, Huang, Xiao-Jun, Qin, Ya-Zhen. 2022. Low IL7R Expression at Diagnosis Predicted Relapse in Adult Acute Myeloid Leukemia Patients With t(8;21). In Frontiers in immunology, 13, 909104. doi:10.3389/fimmu.2022.909104. https://pubmed.ncbi.nlm.nih.gov/35874754/

2. Russell, Jamie, Chen, Luming, Liu, Aijie, Beutler, Bruce, Nair-Gill, Evan. 2024. Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity. In EMBO reports, 25, 3601-3626. doi:10.1038/s44319-024-00191-w. https://pubmed.ncbi.nlm.nih.gov/38956225/

3. Winer, Hila, Rodrigues, Gisele O L, Hixon, Julie A, Li, Wenqing, Durum, Scott K. 2022. IL-7: Comprehensive review. In Cytokine, 160, 156049. doi:10.1016/j.cyto.2022.156049. https://pubmed.ncbi.nlm.nih.gov/36201890/

4. Oliveira, Mariana L, Veloso, Alexandra, Garcia, Elaine G, Langenau, David M, Barata, João T. 2022. Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia. In Leukemia, 36, 1533-1540. doi:10.1038/s41375-022-01590-5. https://pubmed.ncbi.nlm.nih.gov/35581375/

5. Tao, Qiqi, Wu, Qiaoyuan, Xue, Yutong, Liu, Qifa, Jin, Hua. 2024. Prognostic impact of IL7R mutations on acute myeloid leukemia. In Therapeutic advances in hematology, 15, 20406207241279533. doi:10.1177/20406207241279533. https://pubmed.ncbi.nlm.nih.gov/39346679/