The nuclear receptor LXRα controls the functional specialization of splenic macrophages

被引：137

作者：

A-Gonzalez, Noelia ^{[1
,2
]}

Guillen, Jose A. ^{[1
,2
]}

Gallardo, German ^{[2
]}

Diaz, Mercedes ^{[1
,2
]}

de la Rosa, Juan V. ^{[2
]}

Hernandez, Irene H. ^{[1
,2
]}

Casanova-Acebes, Maria ^{[3
]}

Lopez, Felix ^{[2
]}

Tabraue, Carlos ^{[2
]}

Beceiro, Susana ^{[1
,2
]}

Hong, Cynthia ^{[4
]}

Lara, Pedro C. ^{[5
]}

Andujar, Miguel ^{[6
]}

Arai, Satoko ^{[7
]}

Miyazaki, Toru ^{[7
]}

Li, Senlin ^{[8
,9
,10
]}

Corbi, Angel L. ^{[11
]}

Tontonoz, Peter ^{[4
]}

Hidalgo, Andres ^{[3
]}

Castrillo, Antonio ^{[1
,2
]}

机构：

[1] Univ Autonoma Madrid, Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols Madrid, Madrid, Spain

[2] Univ Las Palmas Gran Canaria, Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols Madrid, Unidad Asociada Biomed, Las Palmas Gran Canaria, Spain

[3] Ctr Nacl Invest Cardiovasc, Dept Epidemiol Atherothrombosis & Imaging, Madrid, Spain

[4] Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA

[5] Hosp Univ Gran Canaria Dr Negrin, Serv Oncol Radioterap, Las Palmas Gran Canaria, Spain

[6] Hosp Univ Materno Infantil Las Palmas, Serv Patol, Las Palmas Gran Canaria, Spain

[7] Univ Tokyo, Fac Med, Ctr Dis Biol & Integrat Med, Lab Mol Biomed Pathogenesis, Tokyo 113, Japan

[8] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA

[9] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA

[10] South Texas Vet Hlth Care Syst, San Antonio, TX USA

[11] CSIC, Ctr Invest Biol, Madrid, Spain

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 08期

基金：

美国国家卫生研究院;

关键词：

LIVER X RECEPTORS; GENE-EXPRESSION; MYELOID CELLS; MONOCYTES; METABOLISM; PROLIFERATION; INFLAMMATION; RETENTION; REVEALS; PROTEIN;

D O I：

10.1038/ni.2622

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXR alpha was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXR alpha or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXR alpha-deficient mice. Our results demonstrate that signaling via LXR alpha in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.

引用

页码：831 / +

页数：11

共 47 条

[1] Liver X receptors as regulators of macrophage inflammatory and metabolic pathways [J].