Cutting Edge: Identification and Characterization of Human Intrahepatic CD49a+ NK Cells
Abstract
Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage of hepatic CD49a+DX5− NK cells with adaptive-like features. Development of this NK cell lineage is, in contrast to conventional NK cells, dependent on T-bet but not Eomes. In this study, we describe the identification of a T-bet+Eomes−CD49a+ NK cell subset readily detectable in the human liver, but not in afferent or efferent hepatic venous or peripheral blood. Human intrahepatic CD49a+ NK cells express killer cell Ig-like receptor and NKG2C, indicative of having undergone clonal-like expansion, are CD56bright, and express low levels of CD16, CD57, and perforin. After stimulation, CD49a+ NK cells express high levels of inflammatory cytokines but degranulate poorly. CD49a+ NK cells retain their phenotype after expansion in long-term in vitro cultures. These results demonstrate the presence of a likely human counterpart of mouse intrahepatic NK cells with adaptive-like features.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A subset of liver resident NK (lrNK) has been shown to retain a grade of antigen specificity, called 'memory-like NKs'.
“Intriguingly, a subset of liver resident NK (lrNK) has been shown to retain a grade of antigen specificity. This subset has been called 'memory-like NKs'.”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [75]
Studies on human livers have demonstrated selective expansion of a CD94/NKGC2 pos NK subset upon re-exposure to cytomegalovirus, possessing the ability to produce more IFNγ when exposed to the virus for a second time.
“Studies on human livers have demonstrated the selective expansion of a CD94/NKGC2 pos NK subset upon re-exposure to cytomegalovirus, possessing the ability to produce more IFNγ when exposed to the virus for a second time.(75-77)”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [75]
Cites
Functions of natural killer cells
Vivier, E., Tomasello, E., Baratin, M., Walzer, T., & Ugolini, S. (2008) · Nature Immunology · doi:10.1038/ni1582 · Cited by 3,943 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Natural killer cells in cancer biology and therapy
Wu, S.-Y., Fu, T., Jiang, Y.-Z., & Shao, Z.-M. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01238-x · Cited by 863 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531 · see citing works
Hudspeth, K., Donadon, M., Cimino, M., Pontarini, E., Tentorio, P., Preti, M., Hong, M., Bertoletti, A., Bicciato, S., Invernizzi, P., et al. (2016) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.08.011 · Cited by 246 · see citing works
CXCR6 marks a novel subset of T-betloEomeshi natural killer cells residing in human liver
Stegmann, K. A., Robertson, F., Hansi, N., Gill, U., Pallant, C., Christophides, T., Pallett, L. J., Peppa, D., Dunn, C., Fusai, G., et al. (2016) · Scientific Reports · doi:10.1038/srep26157 · Cited by 235 · see citing works
Mikulak, J., Bruni, E., Oriolo, F., Di Vito, C., & Mavilio, D. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00946 · Cited by 145 · see citing works
Differential Location and Distribution of Hepatic Immune Cells
Freitas-Lopes, M., Mafra, K., David, B., Carvalho-Gontijo, R., & Menezes, G. (2017) · Cells · doi:10.3390/cells6040048 · Cited by 126 · see citing works
Natural killer cells and liver fibrosis
Fasbender, F., Widera, A., Hengstler, J. G., & Watzl, C. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00019 · Cited by 118 · see citing works
Retained NK cell phenotype and functionality in non-alcoholic fatty liver disease
Stiglund, N., Strand, K., Cornillet, M., Stål, P., Thorell, A., Zimmer, C. L., Näslund, E., Karlgren, S., Nilsson, H., Mellgren, G., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01255 · Cited by 72 · see citing works
Self-citationThe liver as a central "hub" of the immune system: pathophysiological implications
Ronca, V., Gerussi, A., Collins, P., Parente, A., Oo, Y. H., & Invernizzi, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00004.2023 · Cited by 59 · see citing works
Immunobiology of primary sclerosing cholangitis
Cornillet, M., Geanon, D., Bergquist, A., & Björkström, N. K. (2025) · Hepatology · doi:10.1097/hep.0000000000001080 · Cited by 20 · see citing works
Self-citationFeng, D. (2020) · Liver Research · doi:10.1016/j.livres.2020.02.003 · Cited by 18 · see citing works
- Authors
- Marquardt, N., Béziat, V., Nyström, S., Hengst, J., Ivarsson, M. A., Kekäläinen, E., Johansson, H., Mjösberg, J., Westgren, M., Lankisch, T. O., Wedemeyer, H., Ellis, E. C., Ljunggren, H.-G., Michaëlsson, J., & Björkström, N. K.
- Affiliations
- Karolinska University Hospital (SE)
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Marquardt, Nicole
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-03
- Volume
- 194
- Issue
- 6
- Pages
- 2467-2471
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2137905106
- Cited by
- 254
- References
- 1
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 15 · 2023: 12 · 2022: 17 · 2021: 28 · 2020: 27 · 2019: 32 · 2018: 21 · 2017: 31 · 2016: 33 · 2015: 16
- FWCI
- 16.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk Fonden (NNF14OC0009347)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- human liver, T-bet, Eomes, NK cell lineage, killer cell immunoglobulin-like receptors, NKG2C, perforin, degranulation, inflammatory cytokines
- MeSH terms
- Adult, Cells, Cultured, Flow Cytometry, Humans, Killer Cells, Natural, Liver, Cytokines, Receptors, IgG, Inflammation Mediators, CD56 Antigen, Integrin alpha1, Cell Proliferation, Receptors, KIR, NK Cell Lectin-Like Receptor Subfamily C
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
