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

• Published in: Allergy (Copenhagen) Vol. 76; no. 9; pp. 2797 - 2808
• Main Authors: Xie, Yanqing, Ju, Xiaotian, Beaudin, Suzanne, Wiltshire, Lesley, Oliveria, John Paul, MacLean, Jonathan, Sommer, Doron D., Cusack, Ruth, Li, Olga, Banerjee, Prajna, Keith, Paul K., O'Byrne, Paul M., Bauer, Rebecca N., Staton, Tracy, Gauvreau, Gail M., Sehmi, Roma
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.09.2021
• Subjects: Adaptive immunity; Allergens; Allergic rhinitis; Allergies; Asthma; CD4 antigen; Cell differentiation; Corticosteroids; Enumeration; Flow cytometry; Histocompatibility antigen HLA; innate lymphoid cells; Leukocytes (eosinophilic); Lymphocytes; Lymphocytes T; Lymphoid cells; Mucosa; nasal challenge; Nose; Placebos; Pruritus; Respiratory tract; Rhinitis; Steroid hormones; Triamcinolone acetonide; type 2 inflammation; asthma; allergic rhinitis; innate lymphoid cells; type 2 inflammation; nasal challenge
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.14835

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. In mild allergic rhinitis with asthma, pre‐treatment with intranasal corticosteroids (INCSs) attenuates allergen‐induced increases in IL‐5/IL‐13+ILC2s, CD4+ T cells and terminal differentiation of EoP in the nasal mucosa with consequent reduction in eosinophilic inflammation. Mucosal ILC2s express HLA‐DR following allergen inhalation challenge; this is reduced by pre‐treatment with INCS treatment. Overnight culture with IL‐2, TSLP or IFN‐γ up‐regulates HLA‐DR expression on ILC2s, in vitro; an effect that is inhibited in the presence of steroids. Abbreviations: EoP, eosinophilic progenitor cell; HLA‐DR, human leukocytes antigen DR; ILCs, innate lymphoid cells