The nuclear receptor LXRα controls the functional specialization of splenic macrophages

Noelia A-Gonzalez, Jose A. Guillen, Germán Gallardo, Mercedes Diaz, Juan V. De La Rosa, Irene H. Hernandez, Maria Casanova-Acebes, Felix Lopez, Carlos Tabraue, Susana Beceiro, Cynthia Hong, Pedro C. Lara, Miguel Andujar, Satoko Arai, Toru Miyazaki, Senlin Li, Angel L. Corbi, Peter Tontonoz, Andres Hidalgo, Antonio Castrillo

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

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 LXRα 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 LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα 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.

Original languageEnglish (US)
Pages (from-to)831-839
Number of pages9
JournalNature Immunology
Volume14
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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