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

(2021) IMMUNITY. 54(9). p.2089-2100
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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.
Keywords
DENDRITIC CELLS, RNA-SEQ, IL-2, LIVER, EXPRESSION, ACTIVATION, INTERLEUKIN-2, RESPONSES, CROSS, FATE

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MLA
De Simone, Giorgia, et al. “Identification of a Kupffer Cell Subset Capable of Reverting the T Cell Dysfunction Induced by Hepatocellular Priming.” IMMUNITY, vol. 54, no. 9, 2021, pp. 2089–100, doi:10.1016/j.immuni.2021.05.005.
APA
De Simone, G., Andreata, F., Bleriot, C., Fumagalli, V., Laura, C., Garcia-Manteiga, J. M., … Iannacone, M. (2021). Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming. IMMUNITY, 54(9), 2089–2100. https://doi.org/10.1016/j.immuni.2021.05.005
Chicago author-date
De Simone, Giorgia, Francesco Andreata, Camille Bleriot, Valeria Fumagalli, Chiara Laura, Jose M. Garcia-Manteiga, Pietro Di Lucia, 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. https://doi.org/10.1016/j.immuni.2021.05.005.
Chicago author-date (all authors)
De Simone, Giorgia, Francesco Andreata, Camille Bleriot, Valeria Fumagalli, Chiara Laura, Jose M. Garcia-Manteiga, Pietro Di Lucia, Stefano Gilotto, Xenia Ficht, Federico Francesco De Ponti, Elisa B. Bono, Leonardo Giustini, Gioia Ambrosi, Marta Mainetti, Paola Zordan, Alexandre P. Benechet, Micol Rava, Svetoslav Chakarov, Federica Moalli, Marc Bajenoff, Luca G. Guidotti, Florent Ginhoux, and Matteo Iannacone. 2021. “Identification of a Kupffer Cell Subset Capable of Reverting the T Cell Dysfunction Induced by Hepatocellular Priming.” IMMUNITY 54 (9): 2089–2100. doi:10.1016/j.immuni.2021.05.005.
Vancouver
1.
De Simone G, Andreata F, Bleriot C, Fumagalli V, Laura C, Garcia-Manteiga JM, et al. Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming. IMMUNITY. 2021;54(9):2089–100.
IEEE
[1]
G. De Simone et al., “Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming,” IMMUNITY, vol. 54, no. 9, pp. 2089–2100, 2021.
@article{8738271,
  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.}},
  author       = {{De Simone, Giorgia and Andreata, Francesco and Bleriot, Camille and Fumagalli, Valeria and Laura, Chiara and Garcia-Manteiga, Jose M. and Di Lucia, Pietro and Gilotto, Stefano and Ficht, Xenia and De Ponti, Federico Francesco and Bono, Elisa B. and Giustini, Leonardo and Ambrosi, Gioia and Mainetti, Marta and Zordan, Paola and Benechet, Alexandre P. and Rava, Micol and Chakarov, Svetoslav and Moalli, Federica and Bajenoff, Marc and Guidotti, Luca G. and Ginhoux, Florent and Iannacone, Matteo}},
  issn         = {{1074-7613}},
  journal      = {{IMMUNITY}},
  keywords     = {{DENDRITIC CELLS,RNA-SEQ,IL-2,LIVER,EXPRESSION,ACTIVATION,INTERLEUKIN-2,RESPONSES,CROSS,FATE}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{2089--2100}},
  title        = {{Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming}},
  url          = {{http://dx.doi.org/10.1016/j.immuni.2021.05.005}},
  volume       = {{54}},
  year         = {{2021}},
}

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