ISM1 protects lung homeostasis via cell-surface GRP78-mediated alveolar macrophage apoptosis.

ABSTRACT: Alveolar macrophages (AMs) are critical for lung immune defense and homeostasis. They are orchestrators of chronic obstructive pulmonary disease (COPD), with their number significantly increased and functions altered in COPD. However, it is unclear how AM number and function are controlled in a healthy lung and if changes in AMs without environmental assault are sufficient to trigger lung inflammation and COPD. We report here that absence of isthmin 1 (ISM1) in mice (Ism1^-/- ) leads to increase in both AM number and functional heterogeneity, with enduring lung inflammation, progressive emphysema, and significant lung function decline, phenotypes similar to human COPD. We reveal that ISM1 is a lung resident anti-inflammatory protein that selectively triggers the apoptosis

SUBMITTER: Lam TYW 

PROVIDER: S-EPMC8794848 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature