Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
Ezrin, an actin-binding protein, orchestrates the organization of the cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. Its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to investigate the contribution of ezrin to monocyte recruitment and adaptation to the lung extracellular matrix (ECM) in response to lipopolysaccharide (LPS). Our study revealed that LPS induces ezrin expression in monocytes/MΦs and is essential for monocytes to adhere to lung ECM, proliferate, and differentiate into tissue-resident interstitial MΦs. Mechanistically, the loss of ezrin in monocytes disrupts activation of focal adhesion kinase and AKT serine-threonine protein kinase signaling, essential for lung-recruited monocytes and monocyte-derived MΦs to adhere to the ECM, proliferate, and survive. In summary, our data show that ezrin plays a role beyond structural cellular support, influencing diverse monocytes/MΦ processes and signaling pathways during inflammation, facilitating their differentiation into tissue-resident macrophages.
Authors
- Toma Tebaldi (ORCID: https://orcid.org/0000-0002-0625-1631)
- Diane S. Krause (ORCID: https://orcid.org/0000-0001-9420-6947)
- Neetu Gupta (ORCID: https://orcid.org/0000-0003-0043-264X)
- Pamela H. Huang
- Emanuela M. Bruscia (ORCID: https://orcid.org/0000-0003-2149-4057)
- Hasan Halit Öz (ORCID: https://orcid.org/0000-0002-5183-5695)
- Adam D. Hoppe (ORCID: https://orcid.org/0000-0003-4180-0840)
- Caterina Di Pietro (ORCID: https://orcid.org/0000-0001-9687-6215)
- Ravindra Gudneppanavar (ORCID: https://orcid.org/0000-0002-9074-8930)
- Stephanie Halene (ORCID: https://orcid.org/0000-0002-2737-9810)
- Giulia Biancon (ORCID: https://orcid.org/0000-0003-0182-7766)
- Catherine Kim (ORCID: https://orcid.org/0000-0003-4780-9213)
- Thomas S. Murray (ORCID: https://orcid.org/0000-0002-6829-7213)
- Marie E. Egan (ORCID: https://orcid.org/0000-0002-0567-6048)
- Anjelica L. Gonzalez (ORCID: https://orcid.org/0000-0003-2082-8764)
- Ee-chun Cheng
- Ping-Xia Zhang
Institutions
- Cleveland Clinic (US)
- South Dakota State University (US)
- University of Trento (IT)
- Yale Cancer Center (US)
- Yale University (US)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2024-11-29
- DOI
- https://doi.org/10.1038/s41419-024-07255-8
- Citations
- 3
- Primary Topic
- Signaling Pathways in Disease
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Cystic Fibrosis Foundation
- Yale University
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- Yale Liver Center