Nmur1, the receptor for neuromedin U (NMU), is a G-protein-coupled receptor. NMU-NMUR1 signaling is involved in multiple biological processes, including mucosal immunity, allergic inflammation, and potentially bone remodeling. It plays a significant role in neuro-immune-epithelial cross-talk, which is crucial for maintaining tissue homeostasis [1,2,3]. Genetic models, such as knockout mice, are valuable for studying its functions.

In gene-targeted mouse models, global knockout of Nmur1 led to reduced ILC2 frequency and effector function, altering transcriptional programs following allergen challenge, thus highlighting its role in allergic inflammation [2]. In ILC2-specific gene-deletion mice generated using the Nmur1 promoter, ILC2-derived AREG promoted non-redundant functions in antiparasite immunity and tissue protection, showing the importance of the Nmur1-driven ILC2-specific gene targeting in understanding immune functions [4]. However, Nmur1 knockout mice had normal inflammation responses in a cutaneous inflammation model, arguing against a major role for Nmur1 in mediating certain inflammatory functions of NmU [5].

In summary, Nmur1 is essential in regulating immune responses, especially those related to ILC2-mediated processes like mucosal immunity and allergic inflammation. The use of Nmur1 knockout and conditional knockout mouse models has provided insights into its functions in these specific disease-relevant biological processes, although its role in some inflammatory responses remains uncertain.

References:

1. Li, Yu, Liu, Shaorui, Zhou, Kewen, He, Danyang, Xu, Heping. 2023. Neuromedin U programs eosinophils to promote mucosal immunity of the small intestine. In Science (New York, N.Y.), 381, 1189-1196. doi:10.1126/science.ade4177. https://pubmed.ncbi.nlm.nih.gov/37708282/

2. Wallrapp, Antonia, Riesenfeld, Samantha J, Burkett, Patrick R, Regev, Aviv, Kuchroo, Vijay K. 2017. The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation. In Nature, 549, 351-356. doi:10.1038/nature24029. https://pubmed.ncbi.nlm.nih.gov/28902842/

3. Hsiao, Yu-Tin, Manikowski, Kelli J, Snyder, Samantha, Allen, Matthew R, Lowery, Jonathan W. 2021. NMUR1 in the NMU-Mediated Regulation of Bone Remodeling. In Life (Basel, Switzerland), 11, . doi:10.3390/life11101028. https://pubmed.ncbi.nlm.nih.gov/34685399/

4. Tsou, Amy M, Yano, Hiroshi, Parkhurst, Christopher N, Lira, Sergio A, Artis, David. 2022. Neuropeptide regulation of non-redundant ILC2 responses at barrier surfaces. In Nature, 611, 787-793. doi:10.1038/s41586-022-05297-6. https://pubmed.ncbi.nlm.nih.gov/36323781/

5. Abbondanzo, Susan J, Manfra, Denise J, Chen, Shu-Cheng, Fine, Jay S, Hedrick, Joseph A. 2008. Nmur1-/- mice are not protected from cutaneous inflammation. In Biochemical and biophysical research communications, 378, 777-82. doi:10.1016/j.bbrc.2008.11.148. https://pubmed.ncbi.nlm.nih.gov/19070594/