期刊
ALLERGY
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1111/all.15918
关键词
airway epithelium; asthma; tezepelumab; virus
Blocking TSLP in asthma patients reduces airway epithelial inflammatory response to viral challenge without affecting anti-viral host resistance.
BackgroundRespiratory 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.AimTo examine effects of blocking TSLP in patients with asthma on host resistance (IFN beta, IFN lambda, and viral load) and on the airway epithelial inflammatory response to viral challenge.MethodsBronchoalveolar 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, IFN beta IFN lambda, and viral load were analyzed by RT-qPCR and multiplex ELISA before and after stimulation.ResultsIL-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 IFN beta and IFN lambda expression and viral load were unchanged.ConclusionBlocking 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.
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