Neuromedin U Induces Pulmonary ILC2 Activation via the NMUR1 Pathway during Acute Respiratory Syncytial Virus Infection.

Abstract

Activated group 2 innate lymphoid cells (ILC2s) play a crucial role in respiratory syncytial virus (RSV)-induced airway inflammation and allergy-like symptoms because of their ability to secrete large quantities of type 2 cytokines. Cytokines such as IL-33, IL-25, and thymic stromal lymphopoietin are activators of ILC2s. Besides, a regulatory effect of neurotransmitters on ILC2 activation has been reported recently. However, whether and how RSV infection induces neurotransmitter production in the lungs and regulates pulmonary ILC2 activation remains unclear. In this study, using a murine model established by intranasal infection with RSV, we found that acute RSV infection induced the production of a neurotransmitter, neuromedin U (NMU), in the lungs of RSV-infected mice and upregulated the expression of NMUR1 (neuromedin U receptor 1) on ILC2s. Moreover, in vivo administration of NMU exacerbated RSV-induced airway inflammation by promoting the proliferation and activation of pulmonary ILC2s via the NMUR1 pathway, which involved PI3K, mitogen-activated protein kinase kinase, and NFAT signaling proteins. Furthermore, pulmonary neurons responded to the stimulation of RSV infection and secreted NMU in a Toll-like receptor 4- and Toll-like receptor 7-dependent manner. Collectively, our data suggest that NMU is a powerful neuropeptide to activate ILC2s, highlighting the critical regulatory effects of neurotransmitters on antiviral, inflammatory, and tissue homeostasis at the mucosal barrier during a viral respiratory infection.

• Authors: Weiwei Liu, Si Wang, Jia Wang, Rui Zheng, Dalu Wang, Rui Yu, Beixing Liu
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 68 Issue 3 Pg. 256-266 (03 2023) ISSN: 1535-4989 [Electronic] United States
• PMID: 36227802 (Publication Type: Journal Article)

Chemical References

• neuromedin U
• Cytokines
• Neuropeptides

Topics

• Animals
• Mice
• Respiratory Syncytial Virus Infections
• Immunity, Innate
• Lymphocytes (metabolism)
• Lung (metabolism)
• Cytokines (metabolism)
• Neuropeptides (metabolism, pharmacology)
• Inflammation
• Respiratory Syncytial Virus, Human