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Mucosal Immunol. 2020 Feb 26. doi: 10.1038/s41385-020-0271-0. [Epub ahead of print]

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

Author information

1
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, 98101, USA.
2
Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
3
Division of Pulmonary and Sleep Medicine, Seattle Children's Hospital, Seattle, WA, 98105, USA.
4
Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA.
5
Department of Immunology, University of Washington School of Medicine, Seattle, WA, 98195, USA.
6
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, 98101, USA. adrian.piliponsky@seattlechildrens.org.
7
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, 98195, USA. adrian.piliponsky@seattlechildrens.org.
8
Department of Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA. adrian.piliponsky@seattlechildrens.org.

Abstract

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.

PMID:
32103153
DOI:
10.1038/s41385-020-0271-0

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