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
  • 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.
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