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Updated: Jun 3, 2026

Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
A signal-responsive cooperative transcription factor network determines alveolar macrophage identity
Jorge Mínguez-Martínez1, Jesús Porcuna1, Laura Casablanca1,2
1Cardiovascular Regeneration Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid, Spain.
Abstract:
Tissue-resident macrophages receive signals from their microenvironment that coordinate the activity of transcription factors (TFs) to establish distinct transcriptional profiles and identities. However, the molecular mechanisms whereby interactions with other cells of the niche imprint a distinct macrophage identity remain poorly understood. Here, we report that retinoid X receptors (RXRs) determine the differentiation and identity of alveolar macrophages (AM) by regulating chromatin accessibility and transcriptional activity of AM-core and function genes, enabling PPARγ-dependent programs. AM differentiation and maintenance in vivo require RXR upregulation in response to tissue-derived δ-like canonical Notch ligand 4 (DLL4), GM-CSF, and TGF β (TGFβ). Interplay among these signals leads to cooperation between RXRα, RBPJ, STAT5, and SMAD4 for the transcriptional and epigenetic regulation of key AM-core genes. These results underscore the role of RXRs as key TFs that cooperate with other regulatory elements to establish the AM population and determine AM identity.
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