I Skrindo1,2, C Ballke1, E Gran3, F-E Johansen1, E S Baekkevold1, F L Jahnsen1. 1. Department of Pathology and Centre for Immune Regulation, Oslo University Hospital and University of Oslo, Oslo, Norway. 2. Department of Otorhinolaryngology, Akershus University Hospital, Lørenskog, Norway. 3. Department of Otolaryngology, Lovisenberg Diakonale Hospital, Oslo, Norway.
Abstract
BACKGROUND: Seasonal allergic rhinitis is a chronic inflammation in the nasal mucosa triggered by inhaled aeroallergens. The inflammatory reaction is controlled by allergen-specific T cells, but where and how these T cells become activated is not fully understood. OBJECTIVES: We wanted to determine whether allergen-specific T-helper (Th) 2 cells are residing in the nasal mucosa under steady-state conditions outside of the pollen season and, if so, whether these cells are activated locally in response to allergen challenge. METHODS: Mucosal biopsies from the lower turbinate were obtained out of season from patients with either birch- or grass-pollen-allergic rhinitis and from healthy controls. Cultured explant samples were challenged with relevant pollen extract or with a mix of overlapping 20-mer peptides derived from the sequence of the major birch allergen, Betula verrucosa (Bet v) 1. After 24 h, culture medium was harvested for multiplex cytokine and tryptase analysis. RESULTS: Significant amounts of interleukin (IL)-5 were secreted from resident cells in response to ex vivo allergen challenge in the allergic group only. No increase was observed for the other cytokines measured. Production of IL-5 in response to both extract and the Bet v1-derived peptide mix strongly suggested that T cells were a major source of IL-5. CONCLUSION: Our explant model indicated that local presentation of antigen to resident allergen-specific Th2 cells is the early event in the pathogenesis of allergic rhinitis. These findings identify possible cellular targets for anti-inflammatory treatment.
BACKGROUND:Seasonal allergic rhinitis is a chronic inflammation in the nasal mucosa triggered by inhaled aeroallergens. The inflammatory reaction is controlled by allergen-specific T cells, but where and how these T cells become activated is not fully understood. OBJECTIVES: We wanted to determine whether allergen-specific T-helper (Th) 2 cells are residing in the nasal mucosa under steady-state conditions outside of the pollen season and, if so, whether these cells are activated locally in response to allergen challenge. METHODS: Mucosal biopsies from the lower turbinate were obtained out of season from patients with either birch- or grass-pollen-allergic rhinitis and from healthy controls. Cultured explant samples were challenged with relevant pollen extract or with a mix of overlapping 20-mer peptides derived from the sequence of the major birch allergen, Betula verrucosa (Bet v) 1. After 24 h, culture medium was harvested for multiplex cytokine and tryptase analysis. RESULTS: Significant amounts of interleukin (IL)-5 were secreted from resident cells in response to ex vivo allergen challenge in the allergic group only. No increase was observed for the other cytokines measured. Production of IL-5 in response to both extract and the Bet v1-derived peptide mix strongly suggested that T cells were a major source of IL-5. CONCLUSION: Our explant model indicated that local presentation of antigen to resident allergen-specific Th2 cells is the early event in the pathogenesis of allergic rhinitis. These findings identify possible cellular targets for anti-inflammatory treatment.
Authors: Siti Muhamad Nur Husna; Norasnieda Md Shukri; Sharifah Emilia Tuan Sharif; Hern Tze Tina Tan; Noor Suryani Mohd Ashari; Kah Keng Wong Journal: Front Mol Biosci Date: 2022-03-17
Authors: Hanif Krabbe; Sergej Klassen; Johannes Bleidorn; Michael J Jacobs; Julia Krabbe; Aaron Babendreyer; Christian Martin Journal: Cells Date: 2021-05-15 Impact factor: 6.600