CCL21-expression and accumulation of CCR7 NK cells in livers of patients with primary sclerosing cholangitis
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CCL21-expression and accumulation of CCR7 NK cells in livers of patients with primary sclerosing cholangitis. / Langeneckert, Annika E; Lunemann, Sebastian; Martrus, Glòria; Salzberger, Wilhelm; Hess, Leonard U; Ziegler, Annerose E; Poch, Tobias; Ravichandran, Gevitha; Matschl, Urte; Bosse, Jens B; Tiegs, Gisa; Fischer, Lutz; Koch, Martina; Herkel, Johannes; Oldhafer, Karl J; Schramm, Christoph; Altfeld, Marcus.
in: EUR J IMMUNOL, Jahrgang 49, Nr. 5, 05.2019, S. 758-769.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - CCL21-expression and accumulation of CCR7 NK cells in livers of patients with primary sclerosing cholangitis
AU - Langeneckert, Annika E
AU - Lunemann, Sebastian
AU - Martrus, Glòria
AU - Salzberger, Wilhelm
AU - Hess, Leonard U
AU - Ziegler, Annerose E
AU - Poch, Tobias
AU - Ravichandran, Gevitha
AU - Matschl, Urte
AU - Bosse, Jens B
AU - Tiegs, Gisa
AU - Fischer, Lutz
AU - Koch, Martina
AU - Herkel, Johannes
AU - Oldhafer, Karl J
AU - Schramm, Christoph
AU - Altfeld, Marcus
N1 - © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2019/5
Y1 - 2019/5
N2 - The pathogenesis of primary sclerosing cholangitis (PSC), an autoimmune liver disease, remains unknown. The aim of this study was to characterize peripheral blood and intrahepatic NK cells from patients with PSC. Peripheral blood samples from patients with PSC, other autoimmune liver diseases, and from healthy control individuals were used, as well as liver tissues from PSC patients undergoing liver transplantation. Multiparameter flow cytometry showed that peripheral blood NK cells from PSC patients were significantly enriched for CCR7 + and CXCR3 + cells, and CCR7 + but not CXCR3 + cells were also significantly increased within intrahepatic NK cells. PSC patients undergoing liver transplantation furthermore had significantly higher plasma levels of the CCR7-ligand CCL21, and the CXCR3-ligands CXCL10 and CXCL11, and significantly higher levels of CCL21, but not CXCL10, were detected in liver tissues. CCR7 + and CXCR3 + NK cells from PSC patients exhibited significantly higher functional capacity in peripheral blood, but not liver tissues, consistent with chronic activation of these NK cells in the inflamed liver. These data show that PSC is characterized by intrahepatic CCL21 expression and accumulation of CCR7 + NK cells in the inflamed liver tissue.
AB - The pathogenesis of primary sclerosing cholangitis (PSC), an autoimmune liver disease, remains unknown. The aim of this study was to characterize peripheral blood and intrahepatic NK cells from patients with PSC. Peripheral blood samples from patients with PSC, other autoimmune liver diseases, and from healthy control individuals were used, as well as liver tissues from PSC patients undergoing liver transplantation. Multiparameter flow cytometry showed that peripheral blood NK cells from PSC patients were significantly enriched for CCR7 + and CXCR3 + cells, and CCR7 + but not CXCR3 + cells were also significantly increased within intrahepatic NK cells. PSC patients undergoing liver transplantation furthermore had significantly higher plasma levels of the CCR7-ligand CCL21, and the CXCR3-ligands CXCL10 and CXCL11, and significantly higher levels of CCL21, but not CXCL10, were detected in liver tissues. CCR7 + and CXCR3 + NK cells from PSC patients exhibited significantly higher functional capacity in peripheral blood, but not liver tissues, consistent with chronic activation of these NK cells in the inflamed liver. These data show that PSC is characterized by intrahepatic CCL21 expression and accumulation of CCR7 + NK cells in the inflamed liver tissue.
KW - Journal Article
U2 - 10.1002/eji.201847965
DO - 10.1002/eji.201847965
M3 - SCORING: Journal article
C2 - 30785638
VL - 49
SP - 758
EP - 769
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 5
ER -
