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Tezepelumab decreas...
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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
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:f6cd482a-13ae-450a-a437-2cfcafb9e503
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https://lup.lub.lu.se/record/f6cd482a-13ae-450a-a437-2cfcafb9e503URI
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https://doi.org/10.1111/all.15918DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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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 ...)
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Cerps, S.Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)sa7111ce
(författare)
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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)
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Ramu, S.Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)med-sru
(författare)
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Hvidtfeldt, M.Bispebjerg Hospital
(författare)
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Menzel, M.Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)med-mym
(författare)
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Kearley, J.AstraZeneca, UK
(författare)
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Griffiths, J. M.AstraZeneca, UK
(författare)
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Parnes, J. R.Amgen Inc.
(författare)
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Porsbjerg, C.Bispebjerg Hospital
(författare)
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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)
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Bispebjerg HospitalRespiratorisk immunofarmakologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Allergy: European Journal of Allergy and Clinical Immunology0105-4538
Internetlänk
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Till lärosätets databas
- Av författaren/redakt...
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Sverrild, A.
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Cerps, S.
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Nieto-Fontarigo, ...
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Ramu, S.
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Hvidtfeldt, M.
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Menzel, M.
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visa fler...
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Kearley, J.
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Griffiths, J. M.
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Parnes, J. R.
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Porsbjerg, C.
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Uller, L.
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