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Updated: Jan 20, 2026

Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation during Idiopathic Pulmonary Fibrosis
Soo Jung Cho1,2, Kyoung Sook Hong1,2,3, Ji Hun Jeong4
1Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10011, USA.
Abstract:
Idiopathic pulmonary fibrosis (IPF) has been linked to chronic lung inflammation. Drosha ribonuclease III (DROSHA), a class 2 ribonuclease III enzyme, plays a key role in microRNA (miRNA) biogenesis. However, the mechanisms by which DROSHA affects the lung inflammation during idiopathic pulmonary fibrosis (IPF) remain unclear. Here, we demonstrate that DROSHA regulates the absent in melanoma 2 (AIM2) inflammasome activation during idiopathic pulmonary fibrosis (IPF). Both DROSHA and AIM2 protein expression were elevated in alveolar macrophages of patients with IPF. We also found that DROSHA and AIM2 protein expression were increased in alveolar macrophages of lung tissues in a mouse model of bleomycin-induced pulmonary fibrosis. DROSHA deficiency suppressed AIM2 inflammasome-dependent caspase-1 activation and interleukin (IL)-1β and IL-18 secretion in primary mouse alveolar macrophages and bone marrow-derived macrophages (BMDMs). Transduction of microRNA (miRNA) increased the formation of the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks, which is required for AIM2 inflammasome activation in BMDMs. Our results suggest that DROSHA promotes AIM2 inflammasome activation-dependent lung inflammation during IPF.
Insights
Drosha ribonuclease III (DROSHA) regulates the absent in melanoma 2 (AIM2) inflammasome, a key driver of lung inflammation in idiopathic pulmonary fibrosis (IPF). This study reveals DROSHA
Area of Science:
- Molecular Biology
- Immunology
- Pulmonary Medicine
Background:
- Idiopathic pulmonary fibrosis (IPF) involves chronic lung inflammation.
- Drosha ribonuclease III (DROSHA) is crucial for microRNA (miRNA) biogenesis.
- The role of DROSHA in IPF-related lung inflammation is not fully understood.
Purpose of the Study:
- To investigate the role of DROSHA in regulating absent in melanoma 2 (AIM2) inflammasome activation in idiopathic pulmonary fibrosis (IPF).
- To elucidate the mechanisms by which DROSHA influences lung inflammation in IPF.
Main Methods:
- Assessed DROSHA and AIM2 protein expression in alveolar macrophages from IPF patients and a mouse model of bleomycin-induced pulmonary fibrosis.
- Evaluated the impact of DROSHA deficiency on AIM2 inflammasome activation, caspase-1 cleavage, and cytokine secretion (IL-1β, IL-18) in macrophages.
- Investigated the effect of miRNA transduction on ASC speck formation and AIM2 inflammasome activation.
Main Results:
- Elevated DROSHA and AIM2 protein levels were observed in alveolar macrophages of IPF patients and in a mouse model.
- DROSHA deficiency attenuated AIM2 inflammasome activation, caspase-1 cleavage, and IL-1β/IL-18 secretion.
- miRNA transduction promoted ASC speck formation, a prerequisite for AIM2 inflammasome activation.
Conclusions:
- DROSHA plays a significant role in promoting AIM2 inflammasome-dependent lung inflammation in IPF.
- Targeting the DROSHA-AIM2 inflammasome pathway may offer therapeutic strategies for IPF.
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