Glutamine metabolism tunes myeloid responses to drive resolution of inflammation during skin repair

  • Cell Rep. 2026 Mar 24;45(3):117001. doi: 10.1016/j.celrep.2026.117001.
Yiting Xu  1 ,  Maria Fernanda Forni  1 ,  Abigail Benvie  1 ,  Nicole Castano  1 ,  Diane King  2 ,  Qiushi Sun  3 ,  Stephan Siebel  3 ,  Van Anh Tran  4 ,  Richard G Kibbey  5 ,  Kathryn Miller-Jensen  6 ,  Valerie Horsley  7
Affiliations
  • 1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
  • 2. Sunnycrest Bioinformatics, Flemington, NJ 08822, USA.
  • 3. Department of Endocrinology, Yale School of Medicine, New Haven, CT 06520, USA.
  • 4. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 5. Department of Endocrinology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.
  • 6. Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA. Electronic address: [email protected].
  • 7. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: [email protected].
PMID: 41712383 DOI: 10.1016/j.celrep.2026.117001
Abstract

Tissue repair requires inflammation resolution, but the molecular mechanisms involved in vivo are not fully understood. Here, we show that glutamine metabolism suppresses neutrophil recruitment to abrogate inflammation and drive skin wound repair. Integrated metabolomic and transcriptional profiling identified glutamine metabolism as enriched in macrophages during resolution. Dietary depletion studies and conditional deletion of Glutaminase, the enzyme essential for glutamine metabolism, in mouse myeloid cells revealed that macrophages suppress neutrophil recruitment genes during tissue resolution to promote repair. We also found that these genes are upregulated in macrophages in patients with diabetes. Mechanistically, our data reveal that glutamine metabolism in macrophages induces suppressive chromatin remodeling of neutrophil recruitment genes, including Ccl ligands, during resolution of inflammation. These findings highlight the ability of specific metabolites to control cellular communication during tissue repair, with glutamine specifically to suppress neutrophil recruitment to advance inflammation resolution.

Keywords
CP: immunology; CP: metabolism; glutamine; immunology; inflammation; macrophages; metabolism; neutrophils; resolution; skin; tissue repair; wound healing.
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