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Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis

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Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis. / Sebode, Marcial; Wigger, Jennifer; Filpe, Pamela; Fischer, Lutz; Weidemann, Sören; Krech, Till; Weiler-Normann, Christina; Peiseler, Moritz; Hartl, Johannes; Tolosa, Eva; Herkel, Johannes; Schramm, Christoph; Lohse, Ansgar W; Arrenberg, Philomena.

In: FRONT IMMUNOL, Vol. 10, 05.2019, p. 1065.

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

Harvard

Sebode, M, Wigger, J, Filpe, P, Fischer, L, Weidemann, S, Krech, T, Weiler-Normann, C, Peiseler, M, Hartl, J, Tolosa, E, Herkel, J, Schramm, C, Lohse, AW & Arrenberg, P 2019, 'Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis', FRONT IMMUNOL, vol. 10, pp. 1065. https://doi.org/10.3389/fimmu.2019.01065

APA

Sebode, M., Wigger, J., Filpe, P., Fischer, L., Weidemann, S., Krech, T., Weiler-Normann, C., Peiseler, M., Hartl, J., Tolosa, E., Herkel, J., Schramm, C., Lohse, A. W., & Arrenberg, P. (2019). Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis. FRONT IMMUNOL, 10, 1065. https://doi.org/10.3389/fimmu.2019.01065

Vancouver

Sebode M, Wigger J, Filpe P, Fischer L, Weidemann S, Krech T et al. Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis. FRONT IMMUNOL. 2019 May;10:1065. https://doi.org/10.3389/fimmu.2019.01065

Bibtex

@article{1ce56ac7ca4b4f979de6ff1fe82de722,
title = "Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis",
abstract = "Background: Natural Killer T (NKT) cells are CD1d-restricted innate-like T cells that can rapidly release stored cytokines upon recognition of lipid antigens. In mice, type I NKT cells seem to promote liver inflammation, whereas type II NKT cells seem to restrict hepatitis. Here, we aimed at characterizing the role of human type I and type II NKT in patients with autoimmune hepatitis (AIH). Methods: NKT cells were analyzed by flow cytometry in peripheral blood and liver of AIH patients and control groups. α-galactosylceramide-loaded or sulfatide-loaded tetramers were used to detect type I or II NKT cells, respectively. Hepatic CD1d was stained by in situ-hybridization of liver biopsies. Results and Conclusions: Type II NKT cells were more prevalent in human peripheral blood and liver than type I NKT cells. In AIH patients, the frequency of sulfatide-reactive type II NKT cells was significantly increased in peripheral blood (0.11% of peripheral blood leukocytes) and liver (3.78% of intrahepatic leukocytes) compared to healthy individuals (0.05% and 1.82%) and patients with drug-induced liver injury (0.06% and 2.03%; p < 0.05). Intrahepatic type II NKT cells of AIH patients had a different cytokine profile than healthy subjects with an increased frequency of TNFα (77.8% vs. 59.1%, p < 0.05), decreased IFNγ (32.7% vs. 63.0%, p < 0.05) and a complete lack of IL-4 expressing cells (0% vs. 2.1%, p < 0.05). T cells in portal tracts expressed significantly more CD1d-RNA in AIH livers compared to controls. This study supports that in contrast to their assumed protective role in mice, human intrahepatic, sulfatide-reactive type II NKT cells displayed a proinflammatory cytokine profile in patients with AIH. Infiltrating T cells in portal areas of AIH patients overexpressed CD1d and could thereby activate type II NKT cells.",
author = "Marcial Sebode and Jennifer Wigger and Pamela Filpe and Lutz Fischer and S{\"o}ren Weidemann and Till Krech and Christina Weiler-Normann and Moritz Peiseler and Johannes Hartl and Eva Tolosa and Johannes Herkel and Christoph Schramm and Lohse, {Ansgar W} and Philomena Arrenberg",
year = "2019",
month = may,
doi = "10.3389/fimmu.2019.01065",
language = "English",
volume = "10",
pages = "1065",
journal = "FRONT IMMUNOL",
issn = "1664-3224",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis

AU - Sebode, Marcial

AU - Wigger, Jennifer

AU - Filpe, Pamela

AU - Fischer, Lutz

AU - Weidemann, Sören

AU - Krech, Till

AU - Weiler-Normann, Christina

AU - Peiseler, Moritz

AU - Hartl, Johannes

AU - Tolosa, Eva

AU - Herkel, Johannes

AU - Schramm, Christoph

AU - Lohse, Ansgar W

AU - Arrenberg, Philomena

PY - 2019/5

Y1 - 2019/5

N2 - Background: Natural Killer T (NKT) cells are CD1d-restricted innate-like T cells that can rapidly release stored cytokines upon recognition of lipid antigens. In mice, type I NKT cells seem to promote liver inflammation, whereas type II NKT cells seem to restrict hepatitis. Here, we aimed at characterizing the role of human type I and type II NKT in patients with autoimmune hepatitis (AIH). Methods: NKT cells were analyzed by flow cytometry in peripheral blood and liver of AIH patients and control groups. α-galactosylceramide-loaded or sulfatide-loaded tetramers were used to detect type I or II NKT cells, respectively. Hepatic CD1d was stained by in situ-hybridization of liver biopsies. Results and Conclusions: Type II NKT cells were more prevalent in human peripheral blood and liver than type I NKT cells. In AIH patients, the frequency of sulfatide-reactive type II NKT cells was significantly increased in peripheral blood (0.11% of peripheral blood leukocytes) and liver (3.78% of intrahepatic leukocytes) compared to healthy individuals (0.05% and 1.82%) and patients with drug-induced liver injury (0.06% and 2.03%; p < 0.05). Intrahepatic type II NKT cells of AIH patients had a different cytokine profile than healthy subjects with an increased frequency of TNFα (77.8% vs. 59.1%, p < 0.05), decreased IFNγ (32.7% vs. 63.0%, p < 0.05) and a complete lack of IL-4 expressing cells (0% vs. 2.1%, p < 0.05). T cells in portal tracts expressed significantly more CD1d-RNA in AIH livers compared to controls. This study supports that in contrast to their assumed protective role in mice, human intrahepatic, sulfatide-reactive type II NKT cells displayed a proinflammatory cytokine profile in patients with AIH. Infiltrating T cells in portal areas of AIH patients overexpressed CD1d and could thereby activate type II NKT cells.

AB - Background: Natural Killer T (NKT) cells are CD1d-restricted innate-like T cells that can rapidly release stored cytokines upon recognition of lipid antigens. In mice, type I NKT cells seem to promote liver inflammation, whereas type II NKT cells seem to restrict hepatitis. Here, we aimed at characterizing the role of human type I and type II NKT in patients with autoimmune hepatitis (AIH). Methods: NKT cells were analyzed by flow cytometry in peripheral blood and liver of AIH patients and control groups. α-galactosylceramide-loaded or sulfatide-loaded tetramers were used to detect type I or II NKT cells, respectively. Hepatic CD1d was stained by in situ-hybridization of liver biopsies. Results and Conclusions: Type II NKT cells were more prevalent in human peripheral blood and liver than type I NKT cells. In AIH patients, the frequency of sulfatide-reactive type II NKT cells was significantly increased in peripheral blood (0.11% of peripheral blood leukocytes) and liver (3.78% of intrahepatic leukocytes) compared to healthy individuals (0.05% and 1.82%) and patients with drug-induced liver injury (0.06% and 2.03%; p < 0.05). Intrahepatic type II NKT cells of AIH patients had a different cytokine profile than healthy subjects with an increased frequency of TNFα (77.8% vs. 59.1%, p < 0.05), decreased IFNγ (32.7% vs. 63.0%, p < 0.05) and a complete lack of IL-4 expressing cells (0% vs. 2.1%, p < 0.05). T cells in portal tracts expressed significantly more CD1d-RNA in AIH livers compared to controls. This study supports that in contrast to their assumed protective role in mice, human intrahepatic, sulfatide-reactive type II NKT cells displayed a proinflammatory cytokine profile in patients with AIH. Infiltrating T cells in portal areas of AIH patients overexpressed CD1d and could thereby activate type II NKT cells.

U2 - 10.3389/fimmu.2019.01065

DO - 10.3389/fimmu.2019.01065

M3 - SCORING: Journal article

C2 - 31191516

VL - 10

SP - 1065

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -