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http://purl.uniprot.org/citations/35963455http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35963455http://www.w3.org/2000/01/rdf-schema#comment"

Background

Neutrophilic asthma is associated with disease severity and corticosteroid insensitivity. Novel therapies are required to manage this life-threatening asthma phenotype. Programmed cell death protein-1 (PD-1) is a key homeostatic modulator of the immune response for T-cell effector functions.

Objective

We sought to investigate the role of PD-1 in the regulation of acute neutrophilic inflammation in a murine model of airway hyperreactivity (AHR).

Methods

House dust mite was used to induce and compare neutrophilic AHR in wild-type and PD-1 knockout mice. Then, the therapeutic potential of a human PD-1 agonist was tested in a humanized mouse model in which the PD-1 extracellular domain is entirely humanized. Single-cell RNA sequencing and flow cytometry were mainly used to investigate molecular and cellular mechanisms.

Results

PD-1 was highly induced on pulmonary T cells in our inflammatory model. PD-1 deficiency was associated with an increased neutrophilic AHR and high recruitment of inflammatory cells to the lungs. Consistently, PD-1 agonist treatment dampened AHR, decreased neutrophil recruitment, and modulated cytokine production in a humanized PD-1 mouse model. Mechanistically, we demonstrated at the transcriptional and protein levels that the inhibitory effect of PD-1 agonist is associated with the reprogramming of pulmonary effector T cells that showed decreased number and activation.

Conclusions

PD-1 agonist treatment is efficient in dampening neutrophilic AHR and lung inflammation in a preclinical humanized mouse model."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2022.07.022"xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Sharpe A.H."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Fung M."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Howard E."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Akbari O."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Quach C."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Soroosh P."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Hurrell B.P."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Helou D.G."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Painter J.D."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Shafiei-Jahani P."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/author"Eddie Loh Y.H."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/name"J Allergy Clin Immunol"xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/pages"526-538.e8"xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/title"Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells."xsd:string
http://purl.uniprot.org/citations/35963455http://purl.uniprot.org/core/volume"151"xsd:string
http://purl.uniprot.org/citations/35963455http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35963455
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http://purl.uniprot.org/uniprot/#_Q02242-mappedCitation-35963455http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35963455
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http://purl.uniprot.org/uniprot/Q02242http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/35963455
http://purl.uniprot.org/uniprot/Q544F3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/35963455
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