Allergy Asthma Immunol Res.  2020 May;12(3):507-522. 10.4168/aair.2020.12.3.507.

Role of IL-17A in Chronic Rhinosinusitis With Nasal Polyp

Affiliations
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea.
  • 2Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea. jihunmo@gmail.com
  • 3Beckman Laser Institute Korea, Dankook University College of Medicine, Cheonan, Korea.

Abstract

PURPOSE
Th17-associated inflammation is increased in chronic rhinosinusitis with nasal polyp (CRSwNP), and is associated with disease severity and steroid resistance. Overexpressed interleukin (IL)-17A affects CRSwNP by tissue remodeling, eosinophilic accumulation, and neutrophilic infiltration. We aimed to identify the role of IL-17A in CRSwNP and to evaluate the effects of anti-IL-17A blocking antibody on nasal polyp (NP) formation using a murine NP model. Moreover, we sought to investigate whether the inhibition of mechanistic target of the rapamycin (mTOR) signal pathway could suppress IL-17A expression and NP formation.
METHODS
Human sinonasal tissues from control subjects and patients with chronic rhinosinusitis (CRS) were analyzed using immunohistochemistry (IHC) and immunofluorescence staining. The effects of IL-17A neutralizing antibody and rapamycin were evaluated in a murine NP model. Mouse samples were analyzed using IHC, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay.
RESULTS
IL-17A+ inflammatory cells were significantly increased in number in NP from patients with CRSwNP compared to that in uncinate process tissues from control subjects and patients with CRS without NP or CRSwNP. CD68+ M1 macrophages dominantly expressed IL-17A, followed by neutrophils and T helper cells, in NP tissues. Neutralization of IL-17A effectively reduced the number of NPs, inflammatory cytokines, and IL-17A-producing cells, including M1 macrophages. Inhibition of IL-17A via the mTOR pathway using rapamycin also attenuated NP formation and inflammation in the murine NP model.
CONCLUSIONS
IL-17A possibly plays a role in the pathogenesis of CRSwNP, the major cellular source being M1 macrophage in NP tissues. Targeting IL-17A directly or indirectly may be an effective therapeutic strategy for CRSwNP.

Keyword

Sinusitis; nasal polyps; IL-17A; TNF-α; rapamycin; mice; immunohistochemistry; real-time polymerase chain reaction

MeSH Terms

Animals
Antibodies, Neutralizing
Cytokines
Enzyme-Linked Immunosorbent Assay
Eosinophils
Fluorescent Antibody Technique
Humans
Immunohistochemistry
Inflammation
Interleukin-17*
Interleukins
Macrophages
Mice
Nasal Polyps*
Neutrophils
Real-Time Polymerase Chain Reaction
Signal Transduction
Sinusitis
Sirolimus
T-Lymphocytes, Helper-Inducer
Antibodies, Neutralizing
Cytokines
Interleukin-17
Interleukins
Sirolimus
Full Text Links
  • AAIR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error