Skip to content
DraconiticResearch
Search Sources API
194,164 studies31 sourcesUpdated 5 min ago
Peer-reviewedCC BY 4.0Frontiers in Immunology

Tezepelumab alters airway epithelial transcriptional responses and epithelial–smooth muscle signalling in uncontrolled asthma

  • Sangeetha Ramu1
  • Sara Vázquez-Mera1
  • Mandy Menzel1
  • Samuel Cerps1
  • Juan José Nieto-Fontarigo1,2,3,4
  • Morten Hvidtfeldt5
  • Celeste Porsbjerg5
  • Asger Sverrild5
  • Lena Uller1
5 affiliations
  1. 1Unit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University
  2. 2BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), University of Santiago de Compostela
  3. 3Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS)
  4. 4Aquatic One Health Research Center (ARCUS), Universidade de Santiago de Compostela
  5. 5Department of Respiratory Medicine, University Hospital Bispebjerg
Read full textPDFDOICite

Abstract

Background: Tezepelumab is a monoclonal antibody that targets thymic stromal lymphopoietin (TSLP). It reduces airway hyperresponsiveness, eosinophilia, mucus plugging, and asthma exacerbations, which are commonly caused by viral infections. Although clinical TSLP blockade attenuates virus-induced IL-33 and T2 cytokines in human bronchial epithelial cells (HBECs), the underlying mechanisms remain incompletely understood.

Aim: The aim of this study was to identify transcriptomic changes modulated by tezepelumab in HBECs and determine their downstream remodelling-related effects on bronchial smooth muscle cells (BSMCs).

Methods: HBECs from patients with uncontrolled asthma before and after 12 weeks of tezepelumab ( n = 13) or placebo ( n = 13) were expanded in vitro as submerged monocultures and subsequently exposed to poly(I:C). Transcriptomic profiling was performed, and selected targets were validated at mRNA and/or protein levels. Conditioned media from HBECs were applied to BSMCs to assess the expression of remodelling-associated mediators.

Results: Tezepelumab treatment downregulated S100A8 and S100A9 expression in unstimulated HBECs. Following poly(I:C) stimulation, exploratory transcriptomic analysis identified enrichment of TNF-α/nuclear factor kappa B (NF-κB)-related pathways in placebo-treated HBECs compared with tezepelumab-treated HBECs. Validation analyses showed variable responses across the cohort, with attenuation observed primarily in patients with higher baseline inflammatory responses. In separate gain-of-function experiments, recombinant TSLP enhanced poly(I:C)-induced expression of S100A8, S100A9, TNFSF15, and TRAF1, together with increased NF-κB activation. Furthermore, conditioned media from poly(I:C)-stimulated HBECs collected after tezepelumab treatment induced lower TGF-β2 gene expression in BSMCs than conditioned media from placebo-treated HBECs.

Conclusion: Clinical TSLP blockade by tezepelumab was associated with altered epithelial transcriptional responses and reduced TGF-β2 gene expression in BSMCs exposed to epithelial conditioned media. These findings are hypothesis-generating and provide transcriptional insight into the mechanisms underlying the therapeutic benefits in asthma management.

Related

  1. Helicobacter pylori Outer Membrane Vesicles Engage TLR2 Through NapA to Promote Epithelial Association and Inflammatory Signalling
    Mariaignacia Rubilar, Rosy Brito, Annegrett Palavecino +4
    Journal of Extracellular VesiclesPeer-reviewedCC BYFull textSurgery & anaesthesiaDOAJ
  2. Blood and Urine Transcriptomes Reveal Complementary Host Responses and a Creatinine-Associated Urinary Transcriptional Axis in Sepsis
    Vyacheslav Beloussov, Vitaliy Strochkov, Nurlan Sandybayev +3
    Diagnostics (Basel, Switzerland)Peer-reviewedCC BYFull textGeneral medicineEurope PMC
  3. NRF2 signalling in environmental metal and metalloid neurotoxicity: distinguishing stress responses from functional neuroprotection
    Bolaji Samuel Mesole, Uthman Ademola Yusuf, Alfred Omachonu Okpanachi +2
    Frontiers in ToxicologyPeer-reviewedCC BYFull textPharmacology & toxicologyDOAJ
  4. Epithelial–mesenchymal plasticity is associated with transcriptional variation in regulated cell death and immune signaling programs in lung adenocarcinoma
    Kuiyuan Liu, Jia Liu, Tiebao Meng +2
    Frontiers in cell and developmental biologyPeer-reviewedCC BYFull textOncologyEurope PMCPMC
  5. Tumour Cell-Associated Heterogeneity in Antiviral Immunity Shapes Influenza Responses and Immune-Modulatory Signalling in Lung Cancer
    Mark A. Miles, Isabella Rosano, Stella Liong +4
    CancersPeer-reviewedCC BY 4.0OncologyCrossref

Cite

BibTeXRIS
BibTeX
@article{ramu2026tezepelumab,
  title = {{Tezepelumab alters airway epithelial transcriptional responses and epithelial–smooth muscle signalling in uncontrolled asthma}},
  author = {Sangeetha Ramu and Sara Vázquez-Mera and Mandy Menzel and Samuel Cerps and Juan José Nieto-Fontarigo and Morten Hvidtfeldt and Celeste Porsbjerg and Asger Sverrild and Lena Uller},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1911911},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1911911/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Tezepelumab alters airway epithelial transcriptional responses and epithelial–smooth muscle signalling in uncontrolled asthma
AU  - Sangeetha Ramu
AU  - Sara Vázquez-Mera
AU  - Mandy Menzel
AU  - Samuel Cerps
AU  - Juan José Nieto-Fontarigo
AU  - Morten Hvidtfeldt
AU  - Celeste Porsbjerg
AU  - Asger Sverrild
AU  - Lena Uller
PY  - 2026
DA  - 2026/10/16
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1911911
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1911911/full
AB  - Background: Tezepelumab is a monoclonal antibody that targets thymic stromal lymphopoietin (TSLP). It reduces airway hyperresponsiveness, eosinophilia, mucus plugging, and asthma exacerbations, which are commonly caused by viral infections. Although clinical TSLP blockade attenuates virus-induced IL-33 and T2 cytokines in human bronchial epithelial cells (HBECs), the underlying mechanisms remain incompletely understood.  Aim: The aim of this study was to identify transcriptomic changes modulated by tezepelumab in HBECs and determine their downstream remodelling-related effects on bronchial smooth muscle cells (BSMCs).  Methods: HBECs from patients with uncontrolled asthma before and after 12 weeks of tezepelumab ( n = 13) or placebo ( n = 13) were expanded in vitro as submerged monocultures and subsequently exposed to poly(I:C). Transcriptomic profiling was performed, and selected targets were validated at mRNA and/or protein levels. Conditioned media from HBECs were applied to BSMCs to assess the expression of remodelling-associated mediators.  Results: Tezepelumab treatment downregulated S100A8 and S100A9 expression in unstimulated HBECs. Following poly(I:C) stimulation, exploratory transcriptomic analysis identified enrichment of TNF-α/nuclear factor kappa B (NF-κB)-related pathways in placebo-treated HBECs compared with tezepelumab-treated HBECs. Validation analyses showed variable responses across the cohort, with attenuation observed primarily in patients with higher baseline inflammatory responses. In separate gain-of-function experiments, recombinant TSLP enhanced poly(I:C)-induced expression of S100A8, S100A9, TNFSF15, and TRAF1, together with increased NF-κB activation. Furthermore, conditioned media from poly(I:C)-stimulated HBECs collected after tezepelumab treatment induced lower TGF-β2 gene expression in BSMCs than conditioned media from placebo-treated HBECs.  Conclusion: Clinical TSLP blockade by tezepelumab was associated with altered epithelial transcriptional responses and reduced TGF-β2 gene expression in BSMCs exposed to epithelial conditioned media. These findings are hypothesis-generating and provide transcriptional insight into the mechanisms underlying the therapeutic benefits in asthma management.
SN  - 1664-3224
ER  -