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Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100

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Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100. / Plochg, Bastian F J; Englert, Hanna; Rangaswamy, Chandini; Konrath, Sandra; Malle, Mandy; Lampalzer, Sibylle; Beisel, Claudia; Wollin, Salma; Frye, Maike; Aberle, Jens; Kluwe, Johannes; Renné, Thomas; Mailer, Reiner K.

In: J INTERN MED, Vol. 291, No. 5, 05.2022, p. 648-664.

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

Harvard

Plochg, BFJ, Englert, H, Rangaswamy, C, Konrath, S, Malle, M, Lampalzer, S, Beisel, C, Wollin, S, Frye, M, Aberle, J, Kluwe, J, Renné, T & Mailer, RK 2022, 'Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100', J INTERN MED, vol. 291, no. 5, pp. 648-664. https://doi.org/10.1111/joim.13434

APA

Plochg, B. F. J., Englert, H., Rangaswamy, C., Konrath, S., Malle, M., Lampalzer, S., Beisel, C., Wollin, S., Frye, M., Aberle, J., Kluwe, J., Renné, T., & Mailer, R. K. (2022). Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100. J INTERN MED, 291(5), 648-664. https://doi.org/10.1111/joim.13434

Vancouver

Plochg BFJ, Englert H, Rangaswamy C, Konrath S, Malle M, Lampalzer S et al. Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100. J INTERN MED. 2022 May;291(5):648-664. https://doi.org/10.1111/joim.13434

Bibtex

@article{5e4af990f4054214aff953b85aeffc25,
title = "Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100",
abstract = "OBJECTIVES: Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4+ T cells in cardiovascular disease (CVD). CVD is a major mortality risk for patients with chronic inflammatory liver diseases. However, the impact of liver damage for ApoB100-specific T-cell responses is unknown.METHODS: We identified ApoB100-specific T cells in blood from healthy controls, nonalcoholic fatty liver disease (NAFLD) patients, and CVD patients by activation-induced marker expression and analyzed their differentiation pattern in correlation to the lipid profile and liver damage parameters in a cross-sectional study. To assess the induction of extrahepatic ApoB100-specific T cells upon transient liver damage in vivo, we performed hydrodynamic tail vein injections with diphtheria toxin A (DTA)-encoding plasmid in human ApoB100-transgenic mice.RESULTS: Utilizing immunodominant ApoB100-derived peptides, we found increased ApoB100-specific T-cell populations in NAFLD and CVD patients compared to healthy controls. In a peptide-specific manner, ApoB100 reactivity in healthy controls was accompanied by expression of the regulatory T (Treg)-cell transcription factor FOXP3. In contrast, FOXP3 expression decreased, whereas expression of pro-inflammatory cytokine interleukin (IL)-17A increased in ApoB100-specific T cells from NAFLD and CVD patients. Dyslipidemia and liver damage parameters in blood correlated with reduced FOXP3 expression and elevated IL-17A production in ApoB100-specific T-cell populations, respectively. Moreover, DTA-mediated transient liver damage in human ApoB100-transgenic mice accumulated IL-17a-expressing ApoB100-specific T cells in the periphery.CONCLUSION: Our results show that liver damage promotes pro-inflammatory ApoB100-specific T-cell populations, thereby providing a cellular mechanism for the increased CVD risk in liver disease patients.",
author = "Plochg, {Bastian F J} and Hanna Englert and Chandini Rangaswamy and Sandra Konrath and Mandy Malle and Sibylle Lampalzer and Claudia Beisel and Salma Wollin and Maike Frye and Jens Aberle and Johannes Kluwe and Thomas Renn{\'e} and Mailer, {Reiner K}",
note = "This article is protected by copyright. All rights reserved.",
year = "2022",
month = may,
doi = "10.1111/joim.13434",
language = "English",
volume = "291",
pages = "648--664",
journal = "J INTERN MED",
issn = "0954-6820",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100

AU - Plochg, Bastian F J

AU - Englert, Hanna

AU - Rangaswamy, Chandini

AU - Konrath, Sandra

AU - Malle, Mandy

AU - Lampalzer, Sibylle

AU - Beisel, Claudia

AU - Wollin, Salma

AU - Frye, Maike

AU - Aberle, Jens

AU - Kluwe, Johannes

AU - Renné, Thomas

AU - Mailer, Reiner K

N1 - This article is protected by copyright. All rights reserved.

PY - 2022/5

Y1 - 2022/5

N2 - OBJECTIVES: Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4+ T cells in cardiovascular disease (CVD). CVD is a major mortality risk for patients with chronic inflammatory liver diseases. However, the impact of liver damage for ApoB100-specific T-cell responses is unknown.METHODS: We identified ApoB100-specific T cells in blood from healthy controls, nonalcoholic fatty liver disease (NAFLD) patients, and CVD patients by activation-induced marker expression and analyzed their differentiation pattern in correlation to the lipid profile and liver damage parameters in a cross-sectional study. To assess the induction of extrahepatic ApoB100-specific T cells upon transient liver damage in vivo, we performed hydrodynamic tail vein injections with diphtheria toxin A (DTA)-encoding plasmid in human ApoB100-transgenic mice.RESULTS: Utilizing immunodominant ApoB100-derived peptides, we found increased ApoB100-specific T-cell populations in NAFLD and CVD patients compared to healthy controls. In a peptide-specific manner, ApoB100 reactivity in healthy controls was accompanied by expression of the regulatory T (Treg)-cell transcription factor FOXP3. In contrast, FOXP3 expression decreased, whereas expression of pro-inflammatory cytokine interleukin (IL)-17A increased in ApoB100-specific T cells from NAFLD and CVD patients. Dyslipidemia and liver damage parameters in blood correlated with reduced FOXP3 expression and elevated IL-17A production in ApoB100-specific T-cell populations, respectively. Moreover, DTA-mediated transient liver damage in human ApoB100-transgenic mice accumulated IL-17a-expressing ApoB100-specific T cells in the periphery.CONCLUSION: Our results show that liver damage promotes pro-inflammatory ApoB100-specific T-cell populations, thereby providing a cellular mechanism for the increased CVD risk in liver disease patients.

AB - OBJECTIVES: Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4+ T cells in cardiovascular disease (CVD). CVD is a major mortality risk for patients with chronic inflammatory liver diseases. However, the impact of liver damage for ApoB100-specific T-cell responses is unknown.METHODS: We identified ApoB100-specific T cells in blood from healthy controls, nonalcoholic fatty liver disease (NAFLD) patients, and CVD patients by activation-induced marker expression and analyzed their differentiation pattern in correlation to the lipid profile and liver damage parameters in a cross-sectional study. To assess the induction of extrahepatic ApoB100-specific T cells upon transient liver damage in vivo, we performed hydrodynamic tail vein injections with diphtheria toxin A (DTA)-encoding plasmid in human ApoB100-transgenic mice.RESULTS: Utilizing immunodominant ApoB100-derived peptides, we found increased ApoB100-specific T-cell populations in NAFLD and CVD patients compared to healthy controls. In a peptide-specific manner, ApoB100 reactivity in healthy controls was accompanied by expression of the regulatory T (Treg)-cell transcription factor FOXP3. In contrast, FOXP3 expression decreased, whereas expression of pro-inflammatory cytokine interleukin (IL)-17A increased in ApoB100-specific T cells from NAFLD and CVD patients. Dyslipidemia and liver damage parameters in blood correlated with reduced FOXP3 expression and elevated IL-17A production in ApoB100-specific T-cell populations, respectively. Moreover, DTA-mediated transient liver damage in human ApoB100-transgenic mice accumulated IL-17a-expressing ApoB100-specific T cells in the periphery.CONCLUSION: Our results show that liver damage promotes pro-inflammatory ApoB100-specific T-cell populations, thereby providing a cellular mechanism for the increased CVD risk in liver disease patients.

UR - https://pubmed.ncbi.nlm.nih.gov/34914849/

U2 - 10.1111/joim.13434

DO - 10.1111/joim.13434

M3 - SCORING: Journal article

C2 - 34914849

VL - 291

SP - 648

EP - 664

JO - J INTERN MED

JF - J INTERN MED

SN - 0954-6820

IS - 5

ER -