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Nectin4 is a potential therapeutic target for asthma
Pureun-Haneul Lee1, Seon Muk Choi1, Min Hyeok An1
1Department of Interdisciplinary Program in Biomedical Science Major, Graduate School of Soonchunhyang University, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.
Frontiers in Immunology
|December 2, 2022
Summary
Nectin4 levels are elevated in asthma patients and contribute to airway inflammation via the Src/Rac1 pathway, suggesting Nectin4 as a potential therapeutic target for asthma.
Area of Science:
- Cellular Biology
- Immunology
- Respiratory Medicine
Background:
- Nectins are cell adhesion molecules involved in Ca2+-independent adhesion.
- The role and clinical significance of Nectin4 in asthma remain unexplored.
Purpose of the Study:
- To investigate the role of Nectin4 in airway inflammation.
- To determine the association between Nectin4 and clinical factors in asthma patients.
Main Methods:
- Examined Nectin4 levels in asthmatic patients and controls.
- Utilized Dermatophagoides pteronyssinus 1 (Der p1)-exposed normal human bronchial epithelial (NHBE) cells.
- Employed Nectin4-deficient (Nectin4-/-) and wild-type (WT) mice models with ovalbumin (OVA) sensitization/challenge.
- Investigated the involvement of the Src/Rac1 pathway in Nectin4-mediated asthma pathogenesis.
Main Results:
- Asthma patients exhibited significantly higher plasma Nectin4 levels compared to controls, correlating with specific IgE and lung function.
- Der p1 exposure increased Nectin4/Afadin and Src/Rac1 in NHBE cells, while Nectin4 siRNA reduced these levels.
- OVA-challenged mice showed increased airway inflammation, obstruction, Th2 cytokines, Nectin4, and Src/Rac1; Nectin4 knockdown attenuated these effects.
Conclusions:
- Nectin4 plays a significant role in airway inflammation associated with asthma.
- Nectin4 emerges as a potential therapeutic target for managing asthma.
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