2. Academic Validation
  3. MiR-221-3p Attenuates IL-33-Induced Mast Cell Cytokine Expression by Targeting KIT

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

  • Int Forum Allergy Rhinol. 2025 Mar 25:e23558. doi: 10.1002/alr.23558.
Ruowu Liu 1,  Jiao Zhou 2,  Jing Zhou 1,  Feng Liu 1,  Yafeng Liu 1,  Juan Meng 1,  Luo Ba 3,  Hengyi Xiao 4,  Shixi Liu 1,  Nan Zhang 5,  Claus Bachert 5,  Jintao Du 1
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
  • 2 Department of Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, West China Hospital, Sichuan University, Chengdu, China.
  • 3 Department of Otolaryngology, People's Hospital of Tibet Autonomous Region, Lhasa, China.
  • 4 Department of Aging and Geriatric Medicine, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  • 5 Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Münster, Münster, Germany.
PMID: 40131162 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.

Keywords

CRSwNP; IL‐33; KIT; mast cell; miR‐221‐3p.

Figures
Products