Paucity of type 2 cytokines and atypical IL-5 receptor alpha patterns during established eosinophilic inflammation in seasonal allergic rhinitis
(2026) In Acta Oto-Laryngologica p.1-13- Abstract
BACKGROUND: Seasonal allergic rhinitis (SAR) is viewed as a type 2 (T2) disease driven by the IL-5/IL-5 receptor α (IL-5Rα) and IL-4/IL-13/IL-4 receptor (IL-4R) pathways and the upstream epithelial alarmins IL-33 and TSLP. However, the dynamics and expression patterns of T2-immunity in the nasal mucosa during sustained allergen exposure remain poorly understood.
AIM/OBJECTIVE: To investigate whether traditional T2-cytokine and alarmin expressions persist during sustained, well-developed eosinophilic inflammation in patients with SAR.
METHODS: Twenty patients were examined late in and outside the birch pollen season. Symptoms, blood, nasal secretions, and mucosal biopsies were evaluated. Analyses included multiplex... (More)
BACKGROUND: Seasonal allergic rhinitis (SAR) is viewed as a type 2 (T2) disease driven by the IL-5/IL-5 receptor α (IL-5Rα) and IL-4/IL-13/IL-4 receptor (IL-4R) pathways and the upstream epithelial alarmins IL-33 and TSLP. However, the dynamics and expression patterns of T2-immunity in the nasal mucosa during sustained allergen exposure remain poorly understood.
AIM/OBJECTIVE: To investigate whether traditional T2-cytokine and alarmin expressions persist during sustained, well-developed eosinophilic inflammation in patients with SAR.
METHODS: Twenty patients were examined late in and outside the birch pollen season. Symptoms, blood, nasal secretions, and mucosal biopsies were evaluated. Analyses included multiplex immunohistochemistry, in situ hybridisation, and computerized image analysis to quantify immune cells, cytokine/alarmin-expression, and their receptors, focusing on IL-5Rα.
RESULTS: Late in the season, patients presented increased symptoms, blood/tissue eosinophilia, and elevated basophils, mast cells, and T helper 2 cells, consistent with a T2-phenotype. Unexpectedly, cells expressing IL-4 and IL-5 mRNA were undetectable. Surprisingly, IL-5Rα was abundant on epithelial cells, but not on mucosal eosinophils. Few scattered IL-13HIGH cells were identified. IL-33 expression remained robust but was lower compared with post-seasonal observations.
CONCLUSIONS AND SIGNIFICANCE: Sustained eosinophilic inflammation in SAR may be maintained by non-T2-pathways in established allergic disease, potentially informing future treatment strategies.
(Less)
- author
- Nordström, Franziska U
LU
; Sakellariou, Christina
LU
; Lindö, Caroline
LU
; Siddhuraj, Premkumar
LU
; Jönsson, Jimmie
; Ahlgren, Johan
LU
; Sandén, Caroline
LU
; Lindstedt, Malin
LU
; Greiff, Lennart
LU
and Erjefält, Jonas S
LU
- organization
- publishing date
- 2026-05-20
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Acta Oto-Laryngologica
- pages
- 1 - 13
- publisher
- Taylor & Francis
- external identifiers
-
- pmid:42159314
- ISSN
- 1651-2251
- DOI
- 10.1080/00016489.2026.2670715
- language
- English
- LU publication?
- yes
- id
- fdb7b8bb-2853-4db0-a66d-8bdab7b8971b
- date added to LUP
- 2026-06-05 10:36:50
- date last changed
- 2026-06-05 11:41:58
@article{fdb7b8bb-2853-4db0-a66d-8bdab7b8971b,
abstract = {{<p>BACKGROUND: Seasonal allergic rhinitis (SAR) is viewed as a type 2 (T2) disease driven by the IL-5/IL-5 receptor α (IL-5Rα) and IL-4/IL-13/IL-4 receptor (IL-4R) pathways and the upstream epithelial alarmins IL-33 and TSLP. However, the dynamics and expression patterns of T2-immunity in the nasal mucosa during sustained allergen exposure remain poorly understood.</p><p>AIM/OBJECTIVE: To investigate whether traditional T2-cytokine and alarmin expressions persist during sustained, well-developed eosinophilic inflammation in patients with SAR.</p><p>METHODS: Twenty patients were examined late in and outside the birch pollen season. Symptoms, blood, nasal secretions, and mucosal biopsies were evaluated. Analyses included multiplex immunohistochemistry, in situ hybridisation, and computerized image analysis to quantify immune cells, cytokine/alarmin-expression, and their receptors, focusing on IL-5Rα.</p><p>RESULTS: Late in the season, patients presented increased symptoms, blood/tissue eosinophilia, and elevated basophils, mast cells, and T helper 2 cells, consistent with a T2-phenotype. Unexpectedly, cells expressing IL-4 and IL-5 mRNA were undetectable. Surprisingly, IL-5Rα was abundant on epithelial cells, but not on mucosal eosinophils. Few scattered IL-13HIGH cells were identified. IL-33 expression remained robust but was lower compared with post-seasonal observations.</p><p>CONCLUSIONS AND SIGNIFICANCE: Sustained eosinophilic inflammation in SAR may be maintained by non-T2-pathways in established allergic disease, potentially informing future treatment strategies.</p>}},
author = {{Nordström, Franziska U and Sakellariou, Christina and Lindö, Caroline and Siddhuraj, Premkumar and Jönsson, Jimmie and Ahlgren, Johan and Sandén, Caroline and Lindstedt, Malin and Greiff, Lennart and Erjefält, Jonas S}},
issn = {{1651-2251}},
language = {{eng}},
month = {{05}},
pages = {{1--13}},
publisher = {{Taylor & Francis}},
series = {{Acta Oto-Laryngologica}},
title = {{Paucity of type 2 cytokines and atypical IL-5 receptor alpha patterns during established eosinophilic inflammation in seasonal allergic rhinitis}},
url = {{http://dx.doi.org/10.1080/00016489.2026.2670715}},
doi = {{10.1080/00016489.2026.2670715}},
year = {{2026}},
}