Identification of the organ-specific function of lymphatics: focusing on the neonatal lung
Szoták-Ajtay Kitti
Molecular Medicine Division
Dr. Várnai Péter
SE Élettani Intézet könyvtára
2026-06-23 15:30:00
Cellular and Molecular Physiology
Dr. Hunyady László
Dr. Jakus Zoltán
Dr. Gasparics Ákos
Dr. Vass Réka
Dr. Wiener Zoltán
Dr. Legeza Balázs
Dr. Uzonyi Barbara
The classical function of lymphatics such as maintaining tissue homeostasis and immunosurveillance are well known. However, different organs have profoundly different tissue environments, which require organ-specific lymphatic function and growth. Our aim was to better understand organ specific lymphatic function of the neonatal lung and the organ specific lymphatic growth of the adult skin.
Initially, we focused on identifying which mechanisms besides surfactant contribute to preparing the neonatal lung for the first breath. Recently lymphatic function was revealed as a previously unknown mechanical regulator of prenatal lung compliance which prepares the embryonic lung for inflation at birth. Late gestation embryos perform episodic breathing-like movements called fetal breathing movements (FBMs), but the physiological importance of these events is not clear. In our current study we aimed to characterize the physiological role of FBMs in preparation for air inflation at birth. For our experiments we used Clp1K/K mice, which develop a progressive loss of spinal motor neurons associated with axonal degeneration and denervation of neuromuscular junctions from E16.5 onward serving as an ideal genetic model to test the possible role of FBMs. We confirmed that Clp1K/K newborns showed impaired motor function including FBMs which resulted in fatal respiratory failure after birth. Next, we showed that the alveolar septa are thicker, and the alveolar area is reduced in Clp1K/K late gestation embryos, while the expression of molecular markers of lung development is not affected. Importantly, our results have revealed that Clp1K/K embryos display dilated pulmonary lymphatic vessels and reduced prenatal lymphatic function and impaired lung expansion. Collecting lymphatics in the lung lack smooth muscle cell coverage, our findings suggest a possible mechanism where FBMs stimulate prenatal lymphatic flow in these pulmonary collecting lymphatics to prepare the developing lung for inflation and gas exchange at birth. Moreover, these results raise the possibility that stimulating FBMs during late gestation might be an effective way to reduce the risk of neonatal respiratory failure.
To better understand organ-specific lymphatic function, we aimed to develop an efficient system to induce lymphatic growth in the skin of adult mice. Our results of experiments with nucleoside-modified VEGFC mRNA LNP platform suggest that this is a novel, greatly potent, and safe therapeutic tool which effectively increases lymphatic growth in the skin of adult mice.
