NR4A1 Deletion in Marginal Zone B Cells Exacerbates Atherosclerosis in Mice - Brief Report
Nus Chimeno, Meritxell Edurne (Division of Cardiovascular Medicine. Department of Medicine. University of Cambridge)
Basatemur, Gemma (University of Cambridge)
Galán, María (Institut d'Investigació Biomèdica Sant Pau)
Cros-Brunsó, Laia (University of Cambridge)
Zhao, Tian X. (University of Cambridge)
Masters, Leanne (University of Cambridge)
Harrison, James (University of Cambridge)
Figg, Nicholas (University of Cambridge)
Tsiantoulas, Dimitrios (Medical University of Vienna)
Geissmann, Frederic (Memorial Sloan Kettering Cancer Centre)
Binder, Christoph J. (Medical University of Vienna)
Sage, Andrew P. (University of Cambridge)
Mallat, Ziad (Paris Cardiovascular Research Center)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	NR4A orphan receptors have been well studied in vascular and myeloid cells where they play important roles in the regulation of inflammation in atherosclerosis. NR4A1 (nerve growth factor IB) is among the most highly induced transcription factors in B cells following BCR (B-cell receptor) stimulation. Given that B cells substantially contribute to the development of atherosclerosis, we examined whether NR4A1 regulates B-cell function during atherogenesis. We found that feeding Ldlrmice a Western diet substantially increased Nr4a1 expression in marginal zone B (MZB) cells compared with follicular B cells. We then generated Ldlrmice with complete B- or specific MZB-cell deletion of Nr4a1. Complete B-cell deletion of Nr4a1 led to increased atherosclerosis, which was accompanied by increased T follicular helper cell-germinal center axis response, as well as increased serum total cholesterol and triglycerides levels. Interestingly, specific MZB-cell deletion of Nr4a1 increased atherosclerosis in association with an increased T follicular helper-germinal center response but without any impact on serum cholesterol or triglyceride levels. Nr4a1MZB cells showed decreased PDL1 (programmed death ligand-1) expression, which may have contributed to the enhanced T follicular helper response. Our findings reveal a previously unsuspected role for NR4A1 in the atheroprotective role of MZB cells. A graphic abstract is available for this article.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Animals ; Atherosclerosis ; Cholesterol ; Diet ; Mice ; Western
Publicat a:	Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 40 Núm. 11 (january 2020) , p. 2598-2604, ISSN 1524-4636

DOI: 10.1161/ATVBAHA.120.314607
PMID: 32907369

7 p, 2.1 MB

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