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  • Sverrild, A.Bispebjerg Hospital (författare)

Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma

  • Artikel/kapitelEngelska

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:f6cd482a-13ae-450a-a437-2cfcafb9e503
  • https://lup.lub.lu.se/record/f6cd482a-13ae-450a-a437-2cfcafb9e503URI
  • https://doi.org/10.1111/all.15918DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Background: Respiratory virus infections are main triggers of asthma exacerbations. Tezepelumab, an anti-TSLP mAb, reduces exacerbations in patients with asthma, but the effect of blocking TSLP on host epithelial resistance and tolerance to virus infection is not known. Aim: To examine effects of blocking TSLP in patients with asthma on host resistance (IFNβ, IFNλ, and viral load) and on the airway epithelial inflammatory response to viral challenge. Methods: Bronchoalveolar lavage fluid (BALF, n = 39) and bronchial epithelial cells (BECs) were obtained from patients with uncontrolled asthma before and after 12 weeks of tezepelumab treatment (n = 13) or placebo (n = 13). BECs were cultured in vitro and exposed to the viral infection mimic poly(I:C) or infected by rhinovirus (RV). Alarmins, T2- and pro-inflammatory cytokines, IFNβ IFNλ, and viral load were analyzed by RT-qPCR and multiplex ELISA before and after stimulation. Results: IL-33 expression in unstimulated BECs and IL-33 protein levels in BALF were reduced after 12 weeks of tezepelumab. Further, IL-33 gene and protein levels decreased in BECs challenged with poly(I:C) after tezepelumab whereas TSLP gene expression remained unaffected. Poly(I:C)-induced IL-4, IL-13, and IL-17A release from BECs was also reduced with tezepelumab whereas IFNβ and IFNλ expression and viral load were unchanged. Conclusion: Blocking TSLP with tezepelumab in vivo in asthma reduced the airway epithelial inflammatory response including IL-33 and T2 cytokines to viral challenge without affecting anti-viral host resistance. Our results suggest that blocking TSLP stabilizes the bronchial epithelial immune response to respiratory viruses.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Cerps, S.Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)sa7111ce (författare)
  • Nieto-Fontarigo, J. J.Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups,CIBER de Fisiopatología Obesidad y Nutricion (CIBEROBN),University of Santiago de Compostela,Health Research Institute of Santiago de Compostela (IDIS)(Swepub:lu)ju6174ni (författare)
  • Ramu, S.Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)med-sru (författare)
  • Hvidtfeldt, M.Bispebjerg Hospital (författare)
  • Menzel, M.Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)med-mym (författare)
  • Kearley, J.AstraZeneca, UK (författare)
  • Griffiths, J. M.AstraZeneca, UK (författare)
  • Parnes, J. R.Amgen Inc. (författare)
  • Porsbjerg, C.Bispebjerg Hospital (författare)
  • Uller, L.Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)mphy-lul (författare)
  • Bispebjerg HospitalRespiratorisk immunofarmakologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Allergy: European Journal of Allergy and Clinical Immunology0105-4538

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