The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes

被引：492

作者：

Hanna, Richard N. ^{[1
]}

Carlin, Leo M. ^{[2
]}

Hubbeling, Harper G. ^{[3
]}

Nackiewicz, Dominika ^{[4
]}

Green, Angela M. ^{[1
]}

Punt, Jennifer A. ^{[3
]}

Geissmann, Frederic ^{[2
]}

Hedrick, Catherine C. ^{[1
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA USA

[2] Kings Coll London, Ctr Mol & Cellular Biol Inflammat, London WC2R 2LS, England

[3] Haverford Coll, Dept Biol, Haverford, PA 19041 USA

[4] Univ Lodz, Dept Genet Microorganisms, PL-90131 Lodz, Poland

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 08期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

ORPHAN STEROID-RECEPTOR; NUCLEAR RECEPTORS; DENDRITIC CELLS; NGFI-B; CLONAL DELETION; GROWTH-FACTORS; LYMPH-NODES; T-CELLS; SUBSETS; MACROPHAGES;

D O I：

10.1038/ni.2063

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C(-) monocytes. Ly6C(-) monocytes, which function in a surveillance role in circulation, were absent from Nr4a1(-/-) mice. Normal numbers of myeloid progenitor cells were present in Nr4a1(-/-) mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from Nr4a1(-/-) mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C(-) monocytes remaining in the bone marrow of Nr4a1(-/-) mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C(-) monocytes.

引用

页码：778 / U148

页数：10

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