Il4ra, the interleukin-4 receptor alpha subunit, is crucial in the immune system. It is part of two types of receptors that modulate immune responses differently and is involved in interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, key drivers of type 2 inflammation [1,2]. It plays important roles in the pathologies of asthma, atopy, and other type 2 inflammatory diseases [1,2]. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its function.

In rhabdomyosarcoma (RMS), conditional deletion of Il4ra in genetically-engineered RMS mouse models showed that nullizygosity of Il4ra 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 the latency of engraftment of Il4ra wild-type tumor cells but not Il4ra null tumor cells [3]. In a mouse model of house dust mite (HDM)-induced allergic dermatitis, Il4ra+ monocytes and macrophages were selectively enriched in Il31ra-deficient HDM dermatitis skin, suggesting a role in type 2 inflammatory responses in the skin [4].

In conclusion, Il4ra is essential for immune-related functions, especially in type 2 inflammation pathways. Model-based research, particularly KO mouse models in RMS and allergic dermatitis, has revealed its role in tumor development and regulation of cutaneous type 2 immune responses, respectively. This contributes to our understanding of the underlying mechanisms in these disease areas.

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/

4. Fassett, Marlys S, Braz, Joao M, Castellanos, Carlos A, Basbaum, Allan I, Ansel, K Mark. 2023. IL-31-dependent neurogenic inflammation restrains cutaneous type 2 immune response in allergic dermatitis. In Science immunology, 8, eabi6887. doi:10.1126/sciimmunol.abi6887. https://pubmed.ncbi.nlm.nih.gov/37831760/