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Paucity of type 2 cytokines and atypical IL-5 receptor alpha patterns during established eosinophilic inflammation in seasonal allergic rhinitis

Nordström, Franziska U LU orcid ; Sakellariou, Christina LU orcid ; Lindö, Caroline LU ; Siddhuraj, Premkumar LU ; Jönsson, Jimmie ; Ahlgren, Johan LU ; Sandén, Caroline LU ; Lindstedt, Malin LU orcid ; Greiff, Lennart LU and Erjefält, Jonas S LU (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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
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}},
}