# Interferon regulatory factor 5 involves the pathogenesis of emphysema through NLRP3 and Ly6C expressing cells

## TL;DR

This study shows that a protein called IRF5 contributes to lung damage in emphysema by affecting immune cells and a type of cell death called pyroptosis.

## Contribution

The study reveals a novel role for IRF5 in emphysema pathogenesis via NLRP3-mediated pyroptosis and Ly6C-expressing immune cells.

## Key findings

- Irf5-knockout mice showed reduced alveolar destruction and suppressed NLRP3 expression after cigarette smoke exposure.
- Ly6Chigh monocytes and T cells from Irf5-KO mice attenuated lung damage when transferred to emphysema mice.
- IRF5 expression was significantly elevated in lung tissues from patients with emphysema.

## Abstract

Interferon regulatory factor 5 (IRF5) is a key regulator of inflammatory responses; however, its role in chronic obstructive pulmonary disease remains unknown. A previous study showed increased IRF5 expression in the lungs of cigarette smoke (CS)-induced emphysema. Here we investigated the function of IRF5 in emphysema using Irf5-knockout (KO) mice. Alveolar destruction, inflammatory cell infiltration, cytokine levels and pyroptosis-related gene expression were assessed in CS-induced emphysema. To investigate the role of immune cells, Ly6C++ (Ly6Chigh) monocytes and Ly6Chigh T cells from Irf5-KO mice were introduced into emphysema mice. The correlation between IRF5 levels and emphysema in humans was also evaluated. Irf5-KO mice showed decreased alveolar destruction after CS exposure. NLRP3 expression was suppressed, and gasdermin D cleavage was altered in Irf5-KO mice, suggesting a protective effect against pyroptotic cell death. Moreover, Ly6Chigh monocytes and Ly6Chigh T cells were more abundant in the lungs of Irf5-KO mice after CS exposure, and their transfer attenuated NLRP3 expression and alveolar damage. Furthermore, IRF5 expression was significantly elevated in lung tissues from patients. Our findings highlight IRF5 as a critical regulator of emphysema pathogenesis via NLRP3-mediated pyroptosis and Ly6Chigh-expressing immune cells. Targeting IRF5 may be a potential therapeutic strategy for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is a lung condition often caused by smoking, leading to inflammation and lung damage. This study explores a protein called IRF5, which is involved in inflammation and immune responses, as a potential target for new treatments. Researchers used mice genetically modified to lack IRF5 (Irf5-knockout mice) and exposed them to cigarette smoke to study emphysema. They found that these mice had less lung damage compared with normal mice. The study focused on how IRF5 affects cell death and immune cell behavior in the lungs. They discovered that IRF5 influences the expression of NLRP3, a protein involved in a type of cell death called pyroptosis, and affects immune cells known as Ly6C-expressing macrophages. Results suggest that targeting IRF5 could help reduce lung damage in emphysema by altering immune responses and cell death pathways. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.