The polarizable and reprogrammable identity of Kupffer cells in Nonalcoholic Steatohepatitis

Kupffer cells (KCs) are the resident macrophages of the liver with similar origins to myeloid-derived macrophages. Once differentiated, KCs exhibit distinct cellular machinery capable of longevity and self-renewal, making them a crucial player in promoting effective intrahepatic communication. However, this gets compromised in disease states like Nonalcoholic Steatohepatitis (NASH), where the loss of embryo-derived KCs (EmKCs) is observed. Despite this, other KC-like and KC-derived populations start to form and contribute to a variety of roles in NASH pathogenesis, often adopting a NASH-associated molecular signature. Here we offer a brief overview of recent reports describing KC polarization and reprogramming in the liver. We describe the complexities of KC cellular identity, their proposed ability to reprogram to fibroblast-like and endothelial-like cells, and the potential implications in NASH.