Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming
| Autor: | Xenia Ficht, Marc Bajénoff, Alexandre P. Benechet, Matteo Iannacone, Federica Moalli, Svetoslav Chakarov, José M. Garcia-Manteiga, Paola Zordan, Pietro Di Lucia, Francesco Andreata, Chiara Laura, Luca G. Guidotti, Marta Mainetti, Giorgia De Simone, Camille Blériot, Elisa Bono, Gioia Ambrosi, Leonardo Giustini, Valeria Fumagalli, Stefano Gilotto, Micol Ravà, Federico F. De Ponti, Florent Ginhoux |
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| Přispěvatelé: | Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), IRCCS San Raffaele Scientific Institute [Milan, Italie], Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, Agency for science, technology and research [Singapore] (A*STAR), De Simone, G., Andreata, F., Bleriot, C., Fumagalli, V., Laura, C., Garcia-Manteiga, J. M., Di Lucia, P., Gilotto, S., Ficht, X., De Ponti, F. F., Bono, E. B., Giustini, L., Ambrosi, G., Mainetti, M., Zordan, P., Benechet, A. P., Rava, M., Chakarov, S., Moalli, F., Bajenoff, M., Guidotti, L. G., Ginhoux, F., Iannacone, M., De Simone, G, Andreata, F, Bleriot, C, Fumagalli, V, Laura, C, Garcia-Manteiga, J, Di Lucia, P, Gilotto, S, Ficht, X, De Ponti, F, Bono, E, Giustini, L, Ambrosi, G, Mainetti, M, Zordan, P, Benechet, A, Rava, M, Chakarov, S, Moalli, F, Bajenoff, M, Guidotti, L, Ginhoux, F, Iannacone, M, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Bajenoff, Marc |
| Rok vydání: | 2021 |
| Předmět: |
[SDV]Life Sciences [q-bio]
hepatitis B viru Priming (immunology) CD8-Positive T-Lymphocytes [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ACTIVATION Mice 0302 clinical medicine Immunology and Allergy Cytotoxic T cell Kupffer cells T cell dysfunction RNA-SEQ Antigen Presentation 0303 health sciences tolerance CD8(+) T cells Effector MED/04 - PATOLOGIA GENERALE Kupffer cell imaging Hepatitis B single cell 3. Good health Infectious Diseases medicine.anatomical_structure [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology 030220 oncology & carcinogenesis CD8+ T cell medicine.drug EXPRESSION Interleukin 2 Kupffer Cells Immunology FATE T cells Mice Transgenic Biology + liver Major histocompatibility complex DENDRITIC CELLS Article 03 medical and health sciences Cross-Priming Antigen scRNA-seq Immune Tolerance medicine Animals [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity 030304 developmental biology IL-2 Biology and Life Sciences CD8 CROSS Cancer research biology.protein CD8+ T cells Interleukin-2 interleukin-2 hepatitis B virus RESPONSES |
| Zdroj: | Immunity Immunity, Elsevier, 2021, 54 (9), pp.2089-2100.e8. ⟨10.1016/j.immuni.2021.05.005⟩ Immunity, 2021, 54 (9), pp.2089-2100.e8. ⟨10.1016/j.immuni.2021.05.005⟩ IMMUNITY |
| ISSN: | 1074-7613 1097-4180 |
| Popis: | Summary 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. Graphical abstract Highlights • KCs are required for in vivo reinvigoration of intrahepatically primed T cells by IL-2 • KCs respond to IL-2 and cross-present hepatocellular Ags • Single-cell RNA-seq identifies two distinct populations of KCs • KC2s have enriched IL-2 sensing machinery and Ag presentation capacity De Simone et al. delineate the mechanisms by which hepatocellularly primed HBV-specific CD8+ T cells acquire antiviral effector functions following IL-2 administration. These mechanisms rely on KCs and, in particular, on a hitherto unidentified KC subset, referred to as KC2, that is poised to respond to IL-2 and cross-present viral antigens. |
| Databáze: | OpenAIRE |
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