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

A Sverrild, S Cerps, J J Nieto-Fontarigo, S Ramu, M Hvidtfeldt, M Menzel, J Kearley, J M Griffiths, J R Parnes, C Porsbjerg, L Uller

7 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
TidsskriftAllergy
Vol/bind79
Udgave nummer3
Sider (fra-til)656-666
Antal sider11
ISSN0105-4538
DOI
StatusUdgivet - mar. 2024

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