Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production

Sebastian Lunemann; Annika E Langeneckert; Gloria Martrus; Leonard U Hess; Wilhelm Salzberger; Annerose E Ziegler; Sebastian M Löbl; Tobias Poch; Gevitha Ravichandran; Jürgen Sauter; Alexander H Schmidt; Christoph Schramm; Karl J Oldhafer; Marcus Altfeld; Christian Körner

doi:10.1002/JLB.1MA1118-428R

Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production

Standard

Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production. / Lunemann, Sebastian; Langeneckert, Annika E; Martrus, Gloria; Hess, Leonard U; Salzberger, Wilhelm; Ziegler, Annerose E; Löbl, Sebastian M; Poch, Tobias; Ravichandran, Gevitha; Sauter, Jürgen; Schmidt, Alexander H; Schramm, Christoph; Oldhafer, Karl J; Altfeld, Marcus; Körner, Christian.

In: J LEUKOCYTE BIOL, Vol. 105, No. 6, 06.2019, p. 1331-1340.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lunemann, S, Langeneckert, AE, Martrus, G, Hess, LU, Salzberger, W, Ziegler, AE, Löbl, SM, Poch, T, Ravichandran, G, Sauter, J, Schmidt, AH, Schramm, C, Oldhafer, KJ, Altfeld, M & Körner, C 2019, 'Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production', J LEUKOCYTE BIOL, vol. 105, no. 6, pp. 1331-1340. https://doi.org/10.1002/JLB.1MA1118-428R

APA

Lunemann, S., Langeneckert, A. E., Martrus, G., Hess, L. U., Salzberger, W., Ziegler, A. E., Löbl, S. M., Poch, T., Ravichandran, G., Sauter, J., Schmidt, A. H., Schramm, C., Oldhafer, K. J., Altfeld, M., & Körner, C. (2019). Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production. J LEUKOCYTE BIOL, 105(6), 1331-1340. https://doi.org/10.1002/JLB.1MA1118-428R

Vancouver

Lunemann S, Langeneckert AE, Martrus G, Hess LU, Salzberger W, Ziegler AE et al. Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production. J LEUKOCYTE BIOL. 2019 Jun;105(6):1331-1340. https://doi.org/10.1002/JLB.1MA1118-428R

Bibtex

@article{3f2299a4d1c2483a893a1ad79847ee27,

title = "Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production",

abstract = "NK cells have been implicated to affect the outcome of numerous liver diseases. In particular, members of the killer-cell Ig-like receptor (KIR) family, predominantly expressed by NK cells, have been associated with the outcome of hepatitis C virus infection and clearance of hepatocellular carcinoma. Inhibitory KIRs tune NK cell function through interaction with HLA class I, a process termed education. Nevertheless, the impact of the hepatic environment on NK cell education is incompletely understood. Therefore, we investigated the composition and function of hepatic KIR-expressing NK cells. Matched PBMC and hepatic lymphocytes were isolated from 20 individuals undergoing liver surgery and subsequently phenotypically analyzed for expression of KIRs and markers for tissue residency using flow cytometry. NK cell function was determined by co-culturing NK cells with the target cell line 721.221 and subsequent assessment of CD107a, IFN-γ, and TNF-α expression. Liver-resident CXCR6+ /CD56Bright NK cells lacked KIRs and were predominantly educated through NKG2A, while CXCR6- /CD16+ NK cells expressed KIRs and resembled peripheral blood NK cells. Hepatic NK cells showed lower response rates compared to peripheral blood NK cells; in particular, CXCR6+ NK cells were hyporesponsive to stimulation with target cells. The high proportion of educated NK cells in both subsets indicates the importance of self-inhibitory receptors for the balance between maintenance of self-tolerance and functional readiness. However, the reduced functionality of hepatic NK cells may reflect the impact of the tolerogenic hepatic environment on NK cells irrespective of NK cell education.",

keywords = "Journal Article",

author = "Sebastian Lunemann and Langeneckert, {Annika E} and Gloria Martrus and Hess, {Leonard U} and Wilhelm Salzberger and Ziegler, {Annerose E} and L{\"o}bl, {Sebastian M} and Tobias Poch and Gevitha Ravichandran and J{\"u}rgen Sauter and Schmidt, {Alexander H} and Christoph Schramm and Oldhafer, {Karl J} and Marcus Altfeld and Christian K{\"o}rner",

note = "{\textcopyright}2019 Society for Leukocyte Biology.",

year = "2019",

month = jun,

doi = "10.1002/JLB.1MA1118-428R",

language = "English",

volume = "105",

pages = "1331--1340",

journal = "J LEUKOCYTE BIOL",

issn = "0741-5400",

publisher = "FASEB",

number = "6",

}

RIS

TY - JOUR

T1 - Human liver-derived CXCR6+ NK cells are predominantly educated through NKG2A and show reduced cytokine production

AU - Lunemann, Sebastian

AU - Langeneckert, Annika E

AU - Martrus, Gloria

AU - Hess, Leonard U

AU - Salzberger, Wilhelm

AU - Ziegler, Annerose E

AU - Löbl, Sebastian M

AU - Poch, Tobias

AU - Ravichandran, Gevitha

AU - Sauter, Jürgen

AU - Schmidt, Alexander H

AU - Schramm, Christoph

AU - Oldhafer, Karl J

AU - Altfeld, Marcus

AU - Körner, Christian

PY - 2019/6

Y1 - 2019/6

N2 - NK cells have been implicated to affect the outcome of numerous liver diseases. In particular, members of the killer-cell Ig-like receptor (KIR) family, predominantly expressed by NK cells, have been associated with the outcome of hepatitis C virus infection and clearance of hepatocellular carcinoma. Inhibitory KIRs tune NK cell function through interaction with HLA class I, a process termed education. Nevertheless, the impact of the hepatic environment on NK cell education is incompletely understood. Therefore, we investigated the composition and function of hepatic KIR-expressing NK cells. Matched PBMC and hepatic lymphocytes were isolated from 20 individuals undergoing liver surgery and subsequently phenotypically analyzed for expression of KIRs and markers for tissue residency using flow cytometry. NK cell function was determined by co-culturing NK cells with the target cell line 721.221 and subsequent assessment of CD107a, IFN-γ, and TNF-α expression. Liver-resident CXCR6+ /CD56Bright NK cells lacked KIRs and were predominantly educated through NKG2A, while CXCR6- /CD16+ NK cells expressed KIRs and resembled peripheral blood NK cells. Hepatic NK cells showed lower response rates compared to peripheral blood NK cells; in particular, CXCR6+ NK cells were hyporesponsive to stimulation with target cells. The high proportion of educated NK cells in both subsets indicates the importance of self-inhibitory receptors for the balance between maintenance of self-tolerance and functional readiness. However, the reduced functionality of hepatic NK cells may reflect the impact of the tolerogenic hepatic environment on NK cells irrespective of NK cell education.

AB - NK cells have been implicated to affect the outcome of numerous liver diseases. In particular, members of the killer-cell Ig-like receptor (KIR) family, predominantly expressed by NK cells, have been associated with the outcome of hepatitis C virus infection and clearance of hepatocellular carcinoma. Inhibitory KIRs tune NK cell function through interaction with HLA class I, a process termed education. Nevertheless, the impact of the hepatic environment on NK cell education is incompletely understood. Therefore, we investigated the composition and function of hepatic KIR-expressing NK cells. Matched PBMC and hepatic lymphocytes were isolated from 20 individuals undergoing liver surgery and subsequently phenotypically analyzed for expression of KIRs and markers for tissue residency using flow cytometry. NK cell function was determined by co-culturing NK cells with the target cell line 721.221 and subsequent assessment of CD107a, IFN-γ, and TNF-α expression. Liver-resident CXCR6+ /CD56Bright NK cells lacked KIRs and were predominantly educated through NKG2A, while CXCR6- /CD16+ NK cells expressed KIRs and resembled peripheral blood NK cells. Hepatic NK cells showed lower response rates compared to peripheral blood NK cells; in particular, CXCR6+ NK cells were hyporesponsive to stimulation with target cells. The high proportion of educated NK cells in both subsets indicates the importance of self-inhibitory receptors for the balance between maintenance of self-tolerance and functional readiness. However, the reduced functionality of hepatic NK cells may reflect the impact of the tolerogenic hepatic environment on NK cells irrespective of NK cell education.

KW - Journal Article

U2 - 10.1002/JLB.1MA1118-428R

DO - 10.1002/JLB.1MA1118-428R

M3 - SCORING: Journal article

C2 - 30779432

VL - 105

SP - 1331

EP - 1340

JO - J LEUKOCYTE BIOL

JF - J LEUKOCYTE BIOL

SN - 0741-5400

IS - 6

ER -