A cellular GPS guides monocytes recruitment and differentiation in the lung

Macrophages are vital immune cells found in the lungs and other tissues, where they help preserve organ health.  When these resident cells are depleted, such as during infection or inflammation, blood-derived monocytes are recruited and must differentiate locally to restore the macrophage population. However, the signals that control this process are still not well understood.

The team of Thomas Marichal (WELRI-ULiège), in collaboration with VIB-UGent and the Karolinska Institute, discovered that monocytes rely on the receptor GPR183 to sense metabolic signals in the lung microenvironment, allowing them to locate macrophage niches and differentiate into lung macrophages.  Once macrophages are fully established in the tissue, the receptor is downregulated, indicating that GPR183 functions primarily during the differentiation phase.

These findings, based on advanced mouse models, single-cell RNA sequencing and imaging approaches, reveal a new mechanism by which metabolic signals in tissue niches instruct immune cell fate.

Reference : Bub et al, Sensing of metabolic signals via GPR183 promotes occupation of lung macrophage niches by monocytes, J Exp Med (2026) 223: e20252667