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Updated: Jan 23, 2026

Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
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The transition from monocyte to tissue-resident macrophage requires DHPS

Gustavo E Carrizo1, Pianpian Lin1, Seung Hyun Lee1

  • 1Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Nature
|January 21, 2026
PubMed

Insights

Deoxyhypusine synthase (DHPS) is essential for tissue-resident macrophage (RTM) development and maintenance. DHPS deficiency impairs monocyte differentiation into RTMs, affecting tissue repair and homeostasis.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Tissue-resident macrophages (RTMs) are crucial for tissue homeostasis, originating from embryonic development or differentiating from infiltrating monocytes during injury.
  • The intrinsic mechanisms governing monocyte differentiation into RTMs and RTM maintenance remain largely unknown.
  • Deoxyhypusine synthase (DHPS) modifies the translation factor eIF5A, playing a role in cellular processes.

Purpose of the Study:

  • To investigate the role of deoxyhypusine synthase (DHPS) in the differentiation and maintenance of tissue-resident macrophages (RTMs).
  • To elucidate the cell-intrinsic mechanisms controlling the monocyte-to-RTM transition.

Main Methods:

  • Generated myeloid-specific DHPS-deficient mice (Dhps-ΔM).
  • Performed transcriptional and proteomic analyses on DHPS-deficient macrophages.
  • Utilized ribosome-engaged transcript sequencing to identify translation-dependent mRNAs.
  • Conducted imaging studies of macrophages in vivo.

Main Results:

  • Dhps-ΔM mice exhibited a global deficiency in RTMs across various tissues, with persistent monocyte influx.
  • DHPS deficiency blocked macrophage differentiation into mature RTMs, impacting cell adhesion and signaling pathways.
  • Defective translation of specific mRNAs involved in cell adhesion and signaling was observed in DHPS-deficient macrophages.
  • DHPS-deficient macrophages showed altered morphology, impaired tissue interaction, and defects in efferocytosis and tissue maintenance.

Conclusions:

  • DHPS is a critical enzyme required for the differentiation and maintenance of RTMs from monocyte precursors.
  • A cell-intrinsic, tissue-agnostic pathway involving DHPS regulates the monocyte-to-RTM transition.
  • DHPS-dependent translation is essential for RTM function, including efferocytosis and tissue homeostasis.

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