Discovery of intrahepatic CD103⁺ cDC1/CD8⁺ T_RM protective immune axis against acetaminophen-induced acute liver injury.

ABSTRACT: Understanding the intrahepatic protective immune systems against acetaminophen (APAP)-induced acute liver injury (ALI) is currently limited. Here we reveal that Gram-positive gut-microbiota-derived pathogen-associated molecular patterns promote the CCL2-dependent infiltration of hepatotoxic Ly6C^hi monocytes into the APAP-damaged liver, thus inducing APAP-ALI. Conversely, Gram-negative bacterial pathogen-associated molecular patterns activate hepatic CD103⁺ cDC1s to produce IL-15, which in turn expands intrahepatic tissue-resident memory CD8⁺ T (T_RM) cells and promotes protective immunity against APAP-derived liver injury. APAP-ALI was further exacerbated in Batf3-knockout and Rag1-knockout mice owing to an increased population of intrahepatic Ly6C^hi monocyt

SUBMITTER: Lee J 

PROVIDER: S-EPMC12686067 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature