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Intestinal neuron-associated macrophages in health and disease

Nature Immunology volume 26, pages 1004–1013 (2025)Cite this article

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Abstract

Neuron–macrophage cross-talk in the intestine plays a crucial role in the maintenance of tissue homeostasis and the modulation of immune responses throughout life. Here, we describe how gut neuron–macrophage interactions shift macrophage phenotype and function from early development to adulthood and how this cross-talk modulates the macrophage function in response to infection and inflammation. We highlight how a neural microenvironment instructs a neuron-associated macrophage phenotype in the gut and show that their phenotype may resemble nerve-associated macrophages in other organs. Finally, we note that the loss of neuron-associated macrophages or a shift in their phenotype can contribute to enteric neurodegeneration in the gastrointestinal tract, causing gut motility disorders.

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Fig. 1: Neuron-associated macrophages in development.
Fig. 2: Neuron-associated macrophages in adulthood.
Fig. 3: Neuromodulation of macrophage function in disease.

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Acknowledgements

This work was supported by the European Research Council (ERC) Advanced Grant (ERC- 833816-NEUMACS) to G.B. M.F.V is supported by an EMBO postdoctoral fellowship (ALTF 873-2023).

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Authors and Affiliations

  1. Center of Intestinal Neuro-Immune Interactions, Translational Research Center for GI Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven-University of Leuven, Leuven, Belgium

    Nathalie Stakenborg & Guy Boeckxstaens

  2. Developmental Biology of the Immune System, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany

    Maria Francesca Viola

Authors
  1. Nathalie Stakenborg
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  2. Maria Francesca Viola
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  3. Guy Boeckxstaens
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N.S., M.F.V. and G.B. wrote the manuscript.

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Correspondence to Guy Boeckxstaens.

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Nature Immunology thanks John Grainger and Gerard Eberl for their contribution to the peer review of this work. Primary Handling Editor: S. Houston in collaboration with the Nature Immunology team.

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Stakenborg, N., Viola, M.F. & Boeckxstaens, G. Intestinal neuron-associated macrophages in health and disease. Nat Immunol 26, 1004–1013 (2025). https://doi.org/10.1038/s41590-025-02150-6

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