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

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-17Aproducing 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.

Evaluation of Serum Total Immunoglobulin E, Interleukin-17 and Pentraxin-3 as Biomarkers for Chronic Rhinosinusitis With Nasal Polyposis

“…However, Th17 cells activation are evident in cases of CRSwNP with production of IL-17A, a cytokine playing critical roles in the development of allergic, inflammatory, and autoimmune reactions. 20 In the current study, the serum level of IL-17 was significantly higher in patient group (p < 0.001) with a significant positive correlation with SNOT 22 and Lund Mackay scores (p < 0.001 for both) and polyposis recurrence (p ¼ 0.005) with a significant agreement to diagnose polyposis (p < 0.001). This matches the findings of previous studies including a study comparing a group of 45 patients with CRSwNP and a control group consisting of 45 healthy volunteers.…”

“…Five ml of venous blood were obtained from every participant by sterile venipuncture. Three ml of which were put in a plain tube, left for 15 min to clot at room temperature, centrifuged at 4000 r.p.m for 10 min, and the resulting sera were kept frozen at - 20…”

Increased day‐to‐day fluctuations in exhaled breath profiles after a rhinovirus challenge in asthma

“…It is intriguing that we did find moderate inverse correlations between the magnitude of the increase in eNose fluctuations and the cytokine levels of IL‐1β, IL‐17A, IL‐8, and TNF‐α, and not for any other mediators. As macrophages are abundantly present in the nasal compartment, 33 and M1‐like macrophages are activated by RVs 34 at an early stage, it is likely that M1‐like macrophages gave rise to these cytokine levels, which can lead to neutrophilic inflammation. 35 Allergic asthmatics have reduced numbers of M1‐like macrophages during RV‐induced exacerbations, 36 which may explain the differences in eNose fluctuations.…”

Endotypes of Asian chronic rhinosinusitis with nasal polyps: A narrative review

“…Non-type 2 inflammation in CRSwNP is characterized by type 1 (Th1) or type 3 (Th17) inflammation [33]. Neutrophilic infiltration is predominant and the expression of IFN-γ and IL-17A are increased in non-eosinophilic NP tissues [34]. Neutrophilic inflammation is observed not only in non-eosinophilic NPs but also in eosinophilic NPs with severe inflammation [6].…”