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, Jahrgang 105, Nr. 6, 06.2019, S. 1331-1340.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
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
N1 - ©2019 Society for Leukocyte Biology.
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 -