Thymic stromal lymphopoietin protects in a model of airway damage and inflammation via regulation of caspase-1 activity and apoptosis inhibition

作者：Nicholas J. Shubin, Morgan Clauson, Kerri Niino, Victoria Kasprzak, Avery Tsuha, Eric Guga, Gauri Bhise, Manasa Acharya, Jessica M. Snyder, Jason S. Debley, Steven F. Ziegler, Adrian M. Piliponsky · 发表于：Mucosal Immunology · 年份：2020 · DOI：10.1038/s41385-020-0271-0 · 被引用次数：18 · 研究领域：Dermatology and Skin Diseases、Asthma and respiratory diseases、Allergic Rhinitis and Sensitization

Thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine, exhibits both pro-inflammatory and pro-homeostatic properties depending on the context and tissues in which it is expressed. It remains unknown whether TSLP has a similar dual role in the airways, where TSLP is known to promote allergic inflammation. Here we show that TSLP receptor (TSLPR)-deficient mice (Tslpr−/−) and mice treated with anti-TSLP antibodies exhibited increased airway inflammation and morbidity rates after bleomycin-induced tissue damage. We found that signaling through TSLPR on non-hematopoietic cells was sufficient for TSLP's protective function. Consistent with this finding, we showed that TSLP reduces caspase-1 and caspase-3 activity levels in primary human bronchial epithelial cells treated with bleomycin via Bcl-xL up-regulation. These observations were recapitulated in vivo by observing that Tslpr−/− mice showed reduced Bcl-xL expression that paralleled increased lung caspase-1 and caspase-3 activity levels and IL-1β concentrations in the bronchial-alveolar lavage fluid. Our studies reveal a novel contribution for TSLP in preventing damage-induced airway inflammation.