MiR‐221‐3p Attenuates IL‐33‐Induced Mast Cell Cytokine Expression by Targeting KIT

• Published in: International forum of allergy & rhinology Vol. 15; no. 8; pp. 837 - 850
• Main Authors: Liu, Ruowu, Zhou, Jiao, Zhou, Jing, Liu, Feng, Liu, Yafeng, Meng, Juan, Ba, Luo, Xiao, Hengyi, Liu, Shixi, Zhang, Nan, Bachert, Claus, Du, Jintao
• Format: Journal Article
• Language: English
• Published: United States 01.08.2025
• Subjects: Adult; Cells, Cultured; Chronic Disease; CRSwNP; Cytokines - genetics; Cytokines - metabolism; Female; Humans; IL‐33; Interleukin-33 - metabolism; Male; mast cell; Mast Cells - immunology; Mast Cells - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR‐221‐3p; Nasal Polyps - genetics; Nasal Polyps - immunology; Nasal Polyps - metabolism; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Rhinitis - genetics; Rhinitis - immunology; Rhinitis - metabolism; Sinusitis - genetics; Sinusitis - immunology; Sinusitis - metabolism; mast cell; IL‐33; miR‐221‐3p; CRSwNP; KIT
• ISSN: 2042-6976; 2042-6984
• DOI: 10.1002/alr.23558

ABSTRACT Background Mast cells (MCs) are involved in type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP), which depends on interleukin (IL)‐33 stimulation. MiR‐221 is reported to be an important regulator of MCs, and miR‐221‐3p can be expressed in CRSwNP. However, the role of miR‐221‐3p in CRSwNP is unclear. Methods Ethmoid tissues from control subjects (n = 12) and polyps from patients with CRSwNP (n = 40) were collected. The expression of miR‐221‐3p and cytokines was detected by real‐time quantitative polymerase chain reaction (qPCR). The activation of P65 and ERK was determined by western blotting. The localization of miR‐221‐3p was detected via in situ hybridization combined with immunofluorescence (IF), and its target was identified via a luciferase reporter system. Human MCs were incubated with IL‐33 or stem cell factor. MicroRNA mimics/inhibitor and lentiviral plasmids were used to determine the role of miR‐221‐3p in MCs. Results We observed increased expression of miR‐221‐3p in CRSwNP, and localized its expression in MCs. The expression of miR‐221‐3p was negatively correlated with that of IL‐4, IL‐5, and IL‐13 in CRSwNP. MiR‐221‐3p can be induced by IL‐33 in MCs and plays a negative regulatory role in cytokine expression and signaling pathways in IL‐33‐induced MC activation. As the direct target of miR‐221‐3p, the receptor KIT was negatively correlated with miR‐221‐3p and decreased in CRSwNP. In MCs, KIT is essential for an effective response to IL‐33 stimulation. We here demonstrated that miR‐221‐3p regulates cytokine expression by targeting KIT in IL‐33‐activated MCs. Conclusions MiR‐221‐3p inhibits MC‐dependent type 2 inflammatory conditions, rendering it a negative regulator of CRSwNP.