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 ma

SUBMITTER: Helou DG 

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

REPOSITORIES: biostudies-literature