Identification of a novel neuron-associated macrophage subset in the liver.

Abstract

Neuron-associated macrophages, shortly NAMs, are one of macrophage subsets which exists on peripheral neurons. NAMs have been identified in various organs including the intestine, skin, lung and adipose tissues. NAMs are responsible for maintaining the tissue integrity through protecting neurons and regulating the immune system. We also newly found out a NAM subset in the liver, especially on the portal vein. The portal vein is the most pivotal feeding vessel which transports food-derived nutrients from the gastrointestinal tract to the liver. Periportal NAM (pNAM) may be responsible for maintaining this vascular homeostasis and controlling the nutrient supply, however, the physiological functions remain uncovered. 

To reveal detailed molecular expressions of pNAM, we performed single-cell RNA sequencing and succeeded in identifying the pNAM cluster and its marker molecules. Estimation of physiological functions using differentially expressed genes in pNAM indicated a possibility that pNAM senses intravascular substances. To directly demonstrate this function, we established an intravital multiphoton imaging system for the portal vein. As the result, we successfully visualized uptake of intravascular substances by pNAM. We are currently investigating what happens in neurons after pNAM senses intravascular substances. Our final goal is to elucidate the importance of pNAM-neuron interactions in liver and portal vein function.