Il4ra, the interleukin-4 receptor alpha subunit, is a crucial component in the immune system. It is part of two types of receptors involved in interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling pathways, which play key roles in type 2 inflammation [1,2]. This signaling is fundamental in immune responses, especially those related to atopy and asthma [1]. Genetic models, such as knockout (KO) mouse models, have been valuable in studying its function.

In rhabdomyosarcoma (RMS), conditional deletion of Il4ra in genetically-engineered RMS mouse models altered the latency, site, and/or stage distribution of RMS tumors. In alveolar rhabdomyosarcoma (ARMS), satellite cell co-injection was necessary for Il4ra null tumor cells engraftment, while in embryonal rhabdomyosarcoma (ERMS), satellite cell co-injection decreased latency of engraftment of Il4ra wildtype tumor cells but not Il4ra null tumor cells. These findings suggest that Il4ra is involved in the interaction between RMS tumor cells and normal muscle stem cells during tumor initiation [3].

In conclusion, Il4ra is essential for regulating type 2 inflammation-related immune responses. The use of Il4ra KO mouse models in RMS research has revealed its role in tumor initiation, highlighting its importance in understanding the development of this disease. Such studies contribute to uncovering potential therapeutic targets in Il4ra-mediated RMS progression [3].

References:

1. Danielewicz, Hanna, Dębińska, Anna, Drabik-Chamerska, Anna, Kalita, Danuta, Boznański, Andrzej. . IL4RA gene expression in relation to I50V, Q551R and C-3223T polymorphisms. In Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 30, 17-22. doi:10.17219/acem/127031. https://pubmed.ncbi.nlm.nih.gov/33529503/

2. McCann, Marc R, Kosloski, Matthew P, Xu, Christine, Davis, John D, Kamal, Mohamed A. . Dupilumab: Mechanism of action, clinical, and translational science. In Clinical and translational science, 17, e13899. doi:10.1111/cts.13899. https://pubmed.ncbi.nlm.nih.gov/39080841/

3. Edwards, David W, Kroepfl, Gabrielle M, Jackson, Jacob M, Michalek, Joel E, Keller, Charles. 2024. Developmental and therapeutic implications of IL4ra expression for rhabdomyosarcoma. In Transgenic research, 33, 229-241. doi:10.1007/s11248-024-00390-0. https://pubmed.ncbi.nlm.nih.gov/38851650/