Work

Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer

Year: 2025

Type: article

Abstract: Intravital microscopy has enabled the study of immune dynamics in the pulmonary microvasculature, but many key events remain unseen because they occur in deeper lung regions. We therefore developed a technique for stabilized intravital imaging of bronchovascular cuffs and collecting lymphatics surrounding pulmonary veins in mice. Intravital imaging of pulmonary lymphatics revealed ventilation-dependence of steady-state lung lymph flow and ventilation-independent lymph flow during inflammation. We imaged the rapid exodus of migratory dendritic cells through lung lymphatics following inflammation and measured effects of pharmacologic and genetic interventions targeting chemokine signaling. Intravital imaging also captured lymphatic immune surveillance of lung-metastatic cancers and lymphatic metastasis of cancer cells. To our knowledge, this is the first imaging of lymph flow and leukocyte migration through intact pulmonary lymphatics. This approach will enable studies of protective and maladaptive processes unfolding within the lungs and in other previously inaccessible locations.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20241359

Authors: Simon J. Cleary, Longhui Qiu, Yurim Seo, Peter Baluk, Dan Liu, Nina K. Serwas, Catherine A. Taylor, Dongliang Zhang, Jason G. Cyster, Donald M. McDonald, Matthew F. Krummel, Mark R. Looney

Institutions: University of California, San Francisco, King's College London, UCSF Helen Diller Family Comprehensive Cancer Center, Howard Hughes Medical Institute, Westlake University, University of California San Francisco Medical Center

Language: English

Topic: Lymphatic System and Diseases

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Gladstone Institutes, National Institutes of Health, University of California, San Francisco, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: Angiopoietins in vascular and lymphatic remodeling of airways and lung, Angiopoietin/Tie signaling regulation of vascular leakage in lung inflammation, Mechanisms, consequences, and reversal of abnormalities in lung lymphatics, Diabetes Research Center, G9000176275, Immunomodulation by splenic megakaryocytes and platelets in sepsis, Mechanisms and pathogenicity of SARS-CoV-2-induced neutrophil extracellular traps, The Tumor Microenvironment Niche of Type I conventional Dendritic Cells, Immunobiology of the normal and injured lung, CONTROL OF T CELL SYNAPSE STABILIZATION AND SIGNALING

OpenAlex ID: W4407726038

FWCI: 11.12

Cites: 81

Cited by: 27

Related to: 10