Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive 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 cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity.

De Simone, G., Andreata, F., Bleriot, C., Fumagalli, V., Laura, C., Garcia-Manteiga, J., et al. (2021). Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming. IMMUNITY, 54(9), 2089-2100 [10.1016/j.immuni.2021.05.005].

Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

Andreata F.
Co-primo
;
2021

Abstract

Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive 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 cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity.
Articolo in rivista - Articolo scientifico
CD8+ T cells; hepatitis B virus; imaging; interleukin-2; Kupffer cells; liver; scRNA-seq; single cell; T cell dysfunction; tolerance
English
2021
54
9
2089
2100
open
De Simone, G., Andreata, F., Bleriot, C., Fumagalli, V., Laura, C., Garcia-Manteiga, J., et al. (2021). Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming. IMMUNITY, 54(9), 2089-2100 [10.1016/j.immuni.2021.05.005].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/425701
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