Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100.
apolipoproteins
atherosclerosis
cardiovascular clinical research
immunology
liver disease
Journal
Journal of internal medicine
ISSN: 1365-2796
Titre abrégé: J Intern Med
Pays: England
ID NLM: 8904841
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
pubmed:
17
12
2021
medline:
15
4
2022
entrez:
16
12
2021
Statut:
ppublish
Résumé
Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4 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. 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. 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.
Substances chimiques
Apolipoprotein B-100
0
Forkhead Transcription Factors
0
Interleukin-17
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
648-664Informations de copyright
© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
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