Kupffer cells: Orchestrators of liver physiology

Area of Science:

• Hepatology and Immunology
• Macrophage Biology
• Metabolic Regulation

Background:

• The liver, a central metabolic organ, relies on specialized cells like Kupffer cells (KCs) for homeostasis.
• KCs, liver-resident macrophages, display functional heterogeneity not fully captured by current classification systems.
• KC interactions with hepatocytes are crucial for coordinated physiological regulation.

Purpose of the Study:

• To review current understanding of liver macrophage biology, focusing on KCs.
• To highlight challenges in KC classification and their physiological roles.
• To examine how factors like circadian rhythms, aging, diet, and exercise influence KC function.

Main Methods:

• Literature review of advances in liver macrophage biology.
• Analysis of KC classification systems and surface markers.
• Discussion of KC functional plasticity and regulation by external factors.

Main Results:

• KCs exhibit complex functional heterogeneity beyond classical polarization.
• Existing KC classification systems lack a systematic theoretical framework.
• KC activity is spatiotemporally regulated by circadian rhythms and nutrient signals, impacting liver pathophysiology.

Conclusions:

• Understanding KC classification and dynamic regulation is crucial for interpreting liver physiology and disease.
• KC plasticity and metabolic reprogramming significantly influence liver health.
• Circadian rhythms, aging, diet, and exercise are key modulators of KC function, offering insights into disease mechanisms.