Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma.
Allergy
; 79(3): 656-666, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-37846599
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 (IFNß, 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(IC) or infected by rhinovirus (RV). Alarmins, T2- and pro-inflammatory cytokines, IFNß 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(IC) after tezepelumab whereas TSLP gene expression remained unaffected. Poly(IC)-induced IL-4, IL-13, and IL-17A release from BECs was also reduced with tezepelumab whereas IFNß 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Viroses
/
Anticorpos Monoclonais Humanizados
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article