Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage

Outtz Reed, Hasina and Wang, Liqing and Sonett, Jarrod and Chen, Mei and Yang, Jisheng and Aradi, Petra and Jakus, Zoltán (2019) Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage. JOURNAL OF CLINICAL INVESTIGATION, 130. ISSN 0021-9738


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The lung is a specialized barrier organ that must tightly regulate interstitial fluid clearance and prevent infection in order to maintain effective gas exchange. Lymphatic vessels are important for these functions in other organs, but their roles in the lung have not been fully defined. In the present study, we addressed how the lymphatic vasculature participates in lung homeostasis. Studies using mice carrying a lymphatic reporter allele revealeded that, in contrast to other organs, lung lymphatic collecting vessels lack smooth muscle cells entirely, suggesting that forward lymph flow is highly dependent on movement and changes in pressure associated with respiration. Functional studies using CLEC2-deficient mice in which lymph flow is impaired due to loss of lympho-venous hemostasis or using inducible lung-specific ablation of lymphatic endothelial cells in a lung transplant model revealeded that loss of lymphatic function leads to an inflammatory state characterized by the formation of tertiary lymphoid organs (TLOs). In addition, impaired lymphatic flow in mice resulteds in hypoxia and features of lung injury that resemble emphysema. These findings reveal both a lung-specific mechanism of lymphatic physiology and a lung-specific consequence of lymphatic dysfunction that may contribute to chronic lung diseases that arise in association with TLO formation.

Item Type: Article
Uncontrolled Keywords: Respiration; lymph; vascular biology; pulmonology;
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat
Depositing User: MTMT SWORD
Date Deposited: 05 Apr 2019 10:23
Last Modified: 05 Apr 2019 10:23

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