1. Academic Validation
  2. Neuromedin U Induces Pulmonary ILC2 Activation via the NMUR1 Pathway During Acute RSV Infection

Neuromedin U Induces Pulmonary ILC2 Activation via the NMUR1 Pathway During Acute RSV Infection

  • Am J Respir Cell Mol Biol. 2022 Oct 13. doi: 10.1165/rcmb.2022-0123OC.
Weiwei Liu 1 2 Si Wang 1 Jia Wang 1 Rui Zheng 1 Dalu Wang 3 Rui Yu 4 Beixing Liu 5
Affiliations

Affiliations

  • 1 China Medical University, Pathogenic Microbiology, Shenyang, Liaoning, China.
  • 2 The First Hospital of China Medical University, Anesthesiology, Shenyang, Liaoning, China.
  • 3 Shengjing Hospital of China Medical University, General Surgery, Shenyang, Liaoning, China.
  • 4 Shengjing Hospital of China Medical University, Nephrology, Shenyang, Liaoning, China.
  • 5 China Medical University, Pathogenic Microbiology, Shenyang, Liaoning, China; [email protected].
Abstract

Activated group 2 innate lymphocytes (ILC2s) play a crucial role in respiratory syncytial virus (RSV)-induced airway inflammation and allergy-like symptoms due to their ability to secrete large quantities of type 2 cytokines. Cytokines such as IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) 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 up-regulated the expression of neuromedin U receptor 1 (NMUR1) 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, MEK, and NFAT signaling proteins. Furthermore, pulmonary neurons responded to the stimulation of RSV Infection and secreted NMU in a TLR4- and TLR7-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.

Keywords

NMU, ILC2 activation, NMUR1, RSV.

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