NR4A1 Deletion in Marginal Zone B Cells Exacerbates Atherosclerosis in Mice-Brief Report

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2020 Sep 10

PMID 32907369

Citations 22

Authors

Meritxell Nus

Gemma Basatemur

Maria Galan

Laia Cros-Brunso

Tian X Zhao

Leanne Masters

James Harrison

Nichola Figg

Dimitrios Tsiantoulas

Frederic Geissmann

Christoph J Binder

Andrew P Sage

Ziad Mallat

Affiliations

Soon will be listed here.

Abstract

Objective: 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. Approach and Results: We found that feeding mice a Western diet substantially increased expression in marginal zone B (MZB) cells compared with follicular B cells. We then generated mice with complete B- or specific MZB-cell deletion of . Complete B-cell deletion of 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 increased atherosclerosis in association with an increased T follicular helper-germinal center response but without any impact on serum cholesterol or triglyceride levels. MZB cells showed decreased PDL1 (programmed death ligand-1) expression, which may have contributed to the enhanced T follicular helper response.

Conclusions: Our findings reveal a previously unsuspected role for NR4A1 in the atheroprotective role of MZB cells.

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