RNAseq of Kupffer cells treated with IL2 and purifed Kupffer cells sub-populations (Kupffer Cell 1 and Kupffer Cell 2)

ABSTRACT: Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages long known for their scavenger and phagocytic functions. KCs are also able to present antigen to CD8+ T cells and promote either T cell tolerance or full effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection – where HBV-specific naïve CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction – to identify a subset of KCs (referred to as KC2) that improves the antiviral function of T cells upon exogenous administration of IL-2. Mechanistically, KC2 were found to be both enriched in the IL-2 sensing machinery and poised to productively cross-present hepatocellular antigens in response to this cytokine. Removing MHC-I from all KCs – including KC2 – as well as selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. Together, these findings indicate that, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment and suggest new strategies for boosting T cell immunity in the liver.

ORGANISM(S): Mus musculus

PROVIDER: GSE152211 | GEO | 2021/09/01

REPOSITORIES: GEO