# Integrated gross and microanatomical analysis of the periportal lymphatic system in human liver

## TL;DR

This study is the first to detail the lymphatic system around the hepatic triad in human livers, revealing how lymph fluid and lymphocytes move through this network.

## Contribution

The first detailed visualization of the human intrahepatic periportal lymphatic system and its lymphocyte transport mechanism.

## Key findings

- Lymphatic vessels with blind ends form a network around the hepatic triad.
- Lymph fluid and lymphocytes use an extravascular pathway guided by CCR7/CCL21 signaling.
- India ink and immunostaining confirmed lymphatic fluid dynamics and CCL21 gradients.

## Abstract

Although animal studies have indicated that the periportal lymphatic system is an important intrahepatic lymphatic route, detailed human studies are scarce. We studied the lymphatic pathways and dynamics around Glisson's capsule in human livers.

We performed whole‐mount immunostaining for the liver using podoplanin and CD‐31 to elucidate the lymphatic vessel distribution around the hepatic triad (HT). Next, 5 mL of India ink was injected into the liver parenchyma to observe the lymph fluid dynamics around Glisson's capsule. Lastly, immunohistochemical staining for CCL21, a chemokine important for lymphocyte migration, and its receptor CCR7 was performed to observe the lymphocyte dynamics within Glisson's capsule.

Lymphatic vessels with blind‐ended structures were observed around the peripheral HT. These vessels ran longitudinally, forming a network with numerous blind ends around HT. Ink distribution was observed within gaps and capillary lymphatic vessels in Glisson's capsule. These gaps were CCL21‐positive, and a concentration gradient was observed toward the capillary lymphatic vessels.

The intrahepatic lymphatic fluid enters the capillary lymphatic vessels via the extravascular pathway, and lymphocyte components enter the capillary lymphatic vessels through the CCR7/CCL21 transport system in the extravascular pathway. This is the first study to elucidate the human intrahepatic periportal lymphatic system.

Using whole‐mount immunostaining, Mitsuhashi and colleagues conducted detailed visualization of lymphatic pathways surrounding the hepatic Glisson's capsule in the human liver. Distinct lymphatic structures and lymphocyte transport via CCR7/CCL21 signaling along the extravascular pathway were identified. This is the first study to elucidate the intrahepatic periportal lymphatic system in humans.