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Inhibition of IL-4Rα reduces CCL26 in bronchial epithelial cells from COPD patients

Pesic, Jelena LU ; Nieto Fontarigo, Juan José LU ; Malm Tillgren, Sofia LU orcid ; Miguens, Pablo LU ; Cerps, Samuel LU ; Pardali, Katerina ; Delaney, Stephen and Uller, Lena LU (2025) In ERJ Open Research
Abstract
Background
Anti-IL-4Rα monoclonal antibodies (mAb) improve lung function and decrease the number of exacerbations in patients with COPD type (T) 2 inflammation. However, the involvement of early innate immune responses underlying these treatment effects is not well known. We sought to understand the effect and mechanisms of IL-4Rα mAb treatment on bronchial epithelial cells from COPD patients under T2 inflammatory conditions with and without rhinoviral infection.

Methods
Primary bronchial epithelial cells (BECs) from healthy and COPD patients were grown at air–liquid interface (ALI) and stimulated with IL-4 or IL-13 cytokines in the presence of IL-4Rα mAb. Cells were infected with human rhinovirus 1B (HRV1B) and collected... (More)
Background
Anti-IL-4Rα monoclonal antibodies (mAb) improve lung function and decrease the number of exacerbations in patients with COPD type (T) 2 inflammation. However, the involvement of early innate immune responses underlying these treatment effects is not well known. We sought to understand the effect and mechanisms of IL-4Rα mAb treatment on bronchial epithelial cells from COPD patients under T2 inflammatory conditions with and without rhinoviral infection.

Methods
Primary bronchial epithelial cells (BECs) from healthy and COPD patients were grown at air–liquid interface (ALI) and stimulated with IL-4 or IL-13 cytokines in the presence of IL-4Rα mAb. Cells were infected with human rhinovirus 1B (HRV1B) and collected 24 h after infection. Anti-viral mediators (i.e., interferons (IFN) and pattern recognition receptors (PRR)), as well as chemokine and alarmin expression was measured by RT-qPCR and ELISA.

Results
Treatment with IL-4Rα mAb (100 nM) inhibited eotaxin-3 (CCL26) gene after IL-4/IL-13 induction (p<0.05) in COPD BECs. However, no significant changes in RV-induced IFN-β, PRRs or TSLP gene responses were observed with IL-4/IL-13 stimulation and IL-4Rα mAb treatment. Significant increase in MUC5AC gene expression was observed with both IL-4 and IL-13 stimulation, but it was not reduced with IL-4Rα treatment in BECs.

Conclusions
Inhibition of IL-4Rα reduced CCL26 levels without affecting anti-viral immune responses in bronchial epithelial cells from COPD patients. Inhibition of IL-4Rα reduced IL-4/IL-13 signaling without broadly suppressing the immune system, which might suggest that inhibition of the IL-4Rα pathways may prevent COPD exacerbations through reduction of eosinophil chemotaxis. (Less)
Abstract (Swedish)
Background Anti-interleukin (IL)-4Rα monoclonal antibodies (mAb) improve lung function and decrease
the number of exacerbations in patients with COPD type (T) 2 inflammation. However, the involvement of
early innate immune responses underlying these treatment effects is not well known. We sought to
understand the effect and mechanisms of IL-4Rα mAb treatment on bronchial epithelial cells (BECs) from
COPD patients under T2 inflammatory conditions with and without rhinoviral infection.
Methods Primary BECs from healthy and COPD patients were grown at an air–liquid interface and
stimulated with IL-4 or IL-13 cytokines in the presence of IL-4Rα mAb. Cells were infected with human
rhinovirus 1B and collected 24 h... (More)
Background Anti-interleukin (IL)-4Rα monoclonal antibodies (mAb) improve lung function and decrease
the number of exacerbations in patients with COPD type (T) 2 inflammation. However, the involvement of
early innate immune responses underlying these treatment effects is not well known. We sought to
understand the effect and mechanisms of IL-4Rα mAb treatment on bronchial epithelial cells (BECs) from
COPD patients under T2 inflammatory conditions with and without rhinoviral infection.
Methods Primary BECs from healthy and COPD patients were grown at an air–liquid interface and
stimulated with IL-4 or IL-13 cytokines in the presence of IL-4Rα mAb. Cells were infected with human
rhinovirus 1B and collected 24 h after infection. Antiviral mediators (i.e., interferons (IFNs) and pattern
recognition receptors (PRRs)), as well as chemokine and alarmin expression, was measured by reverse
transcriptase quantitative PCR and ELISA.
Results Treatment with IL-4Rα mAb (100 nM) inhibited the eotaxin-3 (CCL26) gene after IL-4/IL-13
induction (p<0.05) in COPD BECs. However, no significant changes in rhinovirus-induced IFN-β, PRRs
or thymic stromal lymphopoietin gene responses were observed with IL-4/IL-13 stimulation and IL-4Rα
mAb treatment. A significant increase in mucin 5AC gene expression was observed with both IL-4 and IL-
13 stimulation, but it was not reduced with IL-4Rα treatment in BECs.
Conclusions Inhibition of IL-4Rα reduced CCL26 levels without affecting antiviral immune responses in
BECs from COPD patients. Inhibition of IL-4Rα reduced IL-4/IL-13 signalling without broadly
suppressing the immune system, which might suggest that inhibition of the IL-4Rα pathways may prevent
COPD exacerbations through reduction of eosinophil chemotaxis. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
ERJ Open Research
publisher
European Respiratory Society
ISSN
2312-0541
DOI
10.1183/23120541.00813-2024
language
English
LU publication?
yes
id
caae8339-ee72-426f-b77d-491a65d7e967
date added to LUP
2025-05-21 17:11:19
date last changed
2025-05-22 08:09:33
@article{caae8339-ee72-426f-b77d-491a65d7e967,
  abstract     = {{Background<br/>Anti-IL-4Rα monoclonal antibodies (mAb) improve lung function and decrease the number of exacerbations in patients with COPD type (T) 2 inflammation. However, the involvement of early innate immune responses underlying these treatment effects is not well known. We sought to understand the effect and mechanisms of IL-4Rα mAb treatment on bronchial epithelial cells from COPD patients under T2 inflammatory conditions with and without rhinoviral infection.<br/><br/>Methods<br/>Primary bronchial epithelial cells (BECs) from healthy and COPD patients were grown at air–liquid interface (ALI) and stimulated with IL-4 or IL-13 cytokines in the presence of IL-4Rα mAb. Cells were infected with human rhinovirus 1B (HRV1B) and collected 24 h after infection. Anti-viral mediators (i.e., interferons (IFN) and pattern recognition receptors (PRR)), as well as chemokine and alarmin expression was measured by RT-qPCR and ELISA.<br/><br/>Results<br/>Treatment with IL-4Rα mAb (100 nM) inhibited eotaxin-3 (CCL26) gene after IL-4/IL-13 induction (p&lt;0.05) in COPD BECs. However, no significant changes in RV-induced IFN-β, PRRs or TSLP gene responses were observed with IL-4/IL-13 stimulation and IL-4Rα mAb treatment. Significant increase in MUC5AC gene expression was observed with both IL-4 and IL-13 stimulation, but it was not reduced with IL-4Rα treatment in BECs.<br/><br/>Conclusions<br/>Inhibition of IL-4Rα reduced CCL26 levels without affecting anti-viral immune responses in bronchial epithelial cells from COPD patients. Inhibition of IL-4Rα reduced IL-4/IL-13 signaling without broadly suppressing the immune system, which might suggest that inhibition of the IL-4Rα pathways may prevent COPD exacerbations through reduction of eosinophil chemotaxis.}},
  author       = {{Pesic, Jelena and Nieto Fontarigo, Juan José and Malm Tillgren, Sofia and Miguens, Pablo and Cerps, Samuel and Pardali, Katerina and Delaney, Stephen and Uller, Lena}},
  issn         = {{2312-0541}},
  language     = {{eng}},
  publisher    = {{European Respiratory Society}},
  series       = {{ERJ Open Research}},
  title        = {{Inhibition of IL-4Rα reduces CCL26 in bronchial epithelial cells from COPD patients}},
  url          = {{http://dx.doi.org/10.1183/23120541.00813-2024}},
  doi          = {{10.1183/23120541.00813-2024}},
  year         = {{2025}},
}