Il15ra, encoding interleukin-15 receptor alpha, is a crucial component of interleukin-15 (IL15) pro-inflammatory signaling. IL15/IL15RA signaling is involved in various physiological functions. It usually forms a heterotrimer with IL2 receptors IL2RB and IL2RG to regulate the proliferation and differentiation of cytotoxic T cells and NK cells [2]. In addition, it also impacts functions like muscle contractility, overall metabolism, and is present in the circulation and detected in multiple tissues [1].

In an Il15ra whole-body knockout mouse (Il15ra-/-) study, lack of IL15RA decreased bone mineralization in vivo and in isolated primary osteogenic cultures, suggesting a cell-autonomous effect. The Il15ra-/-osteogenic cultures also had a reduced Rankl/Opg mRNA ratio, indicating defective osteoblast/osteoclast coupling. Transcriptome analysis of primary pre-osteoblasts from normal and Il15ra-/-mice identified differentially expressed genes related to metabolism, immune response, bone mineralization, and morphogenesis [1].

In conclusion, Il15ra is essential for multiple biological functions. The Il15ra knockout mouse model has revealed its cell-autonomous role in osteoblast function and bone mineralization, providing insights into the role of IL15RA in skeletal system development and function [1].

References:

1. Loro, Emanuele, Ramaswamy, Girish, Chandra, Abhishek, Shore, Eileen M, Khurana, Tejvir S. 2017. IL15RA is required for osteoblast function and bone mineralization. In Bone, 103, 20-30. doi:10.1016/j.bone.2017.06.003. https://pubmed.ncbi.nlm.nih.gov/28602725/

2. Marra, Pierfrancesco, Mathew, Sumi, Grigoriadis, Anita, Hayday, Adrian, Tutt, Andrew. 2014. IL15RA drives antagonistic mechanisms of cancer development and immune control in lymphocyte-enriched triple-negative breast cancers. In Cancer research, 74, 4908-21. doi:10.1158/0008-5472.CAN-14-0637. https://pubmed.ncbi.nlm.nih.gov/24980552/