Effect of intranasal corticosteroid treatment on allergen‐induced changes in group 2 innate lymphoid cells in allergic rhinitis with mild asthma

Abstract

Background Allergic rhinitis is characterized by rhinorrhea, nasal congestion, sneezing and nasal pruritus. Group 2 innate lymphoid cells (ILC2s), CD4+ T cells and eosinophils in nasal mucosa are increased significantly after nasal allergen challenge (NAC). Effects of intranasal corticosteroids (INCS) on ILC2s remain to be investigated. Methods Subjects (n = 10) with allergic rhinitis and mild asthma were enrolled in a single‐blind, placebo‐controlled, sequential treatment study and treated twice daily with intranasal triamcinolone acetonide (220 µg) or placebo for 14 days, separated by a 7‐day washout period. Following treatment, subjects underwent NAC and upper airway function was assessed. Cells from the nasal mucosa and blood, sampled 24 h post‐NAC, underwent flow cytometric enumeration for ILC2s, CD4+ T and eosinophil progenitor (EoPs) levels. Cell differentials and cytokine levels were assessed in nasal lavage. Results Treatment with INCS significantly attenuated ILC2s, IL‐5+/IL‐13+ILC2s, HLA‐DR+ILC2s and CD4+ T cells in the nasal mucosa, 24 h post‐NAC. EoP in nasal mucosa was significantly increased, while mature eosinophils were significantly decreased, 24 h post‐NAC in INCS versus placebo treatment arm. Following INCS treatment, IL‐2, IL‐4, IL‐5 and IL‐13 were significantly attenuated 24 h post‐NAC accompanied by significant improvement in upper airway function. Conclusion Pre‐treatment with INCS attenuates allergen‐induced increases in ILC2s, CD4+ T cells and terminal differentiation of EoPs in the nasal mucosa of allergic rhinitis patients with mild asthma, with little systemic effect. Attenuation of HLA‐DR expression by ILC2s may be an additional mechanism by which steroids modulate adaptive immune responses in the upper airways.

How an Immune-Factor-Based Formulation of Micro-Immunotherapy Could Interfere with the Physiological Processes Involved in the Atopic March

“…In terms of the role of this cell population and the implication of its HLA-DR expression in allergy and asthma, the results of a single-blind, placebo-controlled clinical study merit our attention. Investigators assessed the effects of the intranasal administration of the triamcinolone acetonide corticosteroid on this ILC2 population [ 147 ]. Interestingly, when assessed 24 h post-nasal-allergen challenge, such treatment significantly decreased IL-5 + /IL-13 + ILC2s, as well as HLA-DR + ILC2 within the nasal mucosa, thus, highlighting the fact that the attenuation of HLA-DR expression by ILC2 may be another mechanism of action of corticosteroids in modulating the adaptive immune responses in airway allergies that MI can exploit.…”

Use of intraoperative frontal sinus mometasone‐eluting stents decreased interleukin 5 and interleukin 13 in patients with chronic rhinosinusitis with nasal polyps

“…These changes may indicate that the release of mometasone for a short duration after surgery may affect ILC2‐dependent production of IL‐5 and IL‐13 over a longer period than anticipated. A recent ex vivo study similarly found that nasal mucosal cells taken from patients pretreated with INCs exhibited decreased numbers of ILC2 as well as the allergen‐induced production of IL‐5 and IL‐13 34 . The T2 endotype is classically associated with eosinophilia and nasal polyposis, while the type 3 endotype is classically associated with neutrophilia and the presence of purulence 35 …”

“…A recent ex vivo study similarly found that nasal mucosal cells taken from patients pretreated with INCs exhibited decreased numbers of ILC2 as well as the allergen-induced production of IL-5 and IL-13. 34 The T2 endotype is classically associated with eosinophilia and nasal polyposis, while the type 3 endotype is classically associated with neutrophilia and the presence of purulence. 35 Given the observed differences in concentrations of MM T2 mediators, we evaluated whether patients who did and did not receive MES at the pre-ESS and post-ESS time points were similar.…”

“…A recent ex vivo study similarly found that nasal mucosal cells taken from patients pretreated with INCs exhibited decreased numbers of ILC2 as well as the allergen‐induced production of IL‐5 and IL‐13. 34 The T2 endotype is classically associated with eosinophilia and nasal polyposis, while the type 3 endotype is classically associated with neutrophilia and the presence of purulence. 35 …”

The role of hypoxia in the pathophysiology of chronic rhinosinusitis

“…T cells are derived from bone marrow lymphoid stem cells, which differentiate and mature in the thymus, and subsequently play an immune role in various different organs and tissues. [169][170][171][172][173] T cells are also involved in upper respiratory tract diseases and have, in recent years, been found to be affected by hypoxia. Hypoxia activates HIF-1α to enhance the inflammatory response induced by CD8 + type 2 cytotoxic T cells (T C 2) in asthma.…”