Dataset Information

Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells.

ABSTRACT:

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.

SUBMITTER: Helou DG

PROVIDER: S-EPMC9905221 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells.

Helou Doumet Georges DG Quach Christine C Fung Marshall M Painter Jacob D JD Hurrell Benjamin P BP Eddie Loh Yong-Hwee YH Howard Emily E Shafiei-Jahani Pedram P Soroosh Pejman P Sharpe Arlene H AH Akbari Omid O

The Journal of allergy and clinical immunology 20220811 2

<h4>Background</h4>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.<h4>Objective</h4>We sought to investigate the role of PD-1 in the regulation of acute neutrophilic inflammation in a murine model of airway hyperreactivity (AHR).<h4>Methods</h4>House dust ...[more]

PMID: 35963455

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Dataset Information

Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells.

Background

Objective

Methods

Results

Conclusions

Publications

Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells.

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