ARG1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting.

Authors

Lexing Li, Guoyan Zhu, Mengdie Chen, Bingqing Qiu, Yujia Li, Shiyu Liu, Wei Gu, Leilei Liu

Published in

Frontiers in immunology. Volume 17. Pages 1744890. Epub Mar 19, 2026.

Abstract

ARG1 catalyzes the conversion of L-arginine to L-ornithine, urea, polyamines, and L-proline, thereby balancing nitrogen detoxification with tissue-specific roles in proliferation and immunity. This review delineates the context-dependent functions of ARG1 across diverse cell types-including tumor cells, immune cells, endothelial cells, keratinocytes, and stem cells. In tumors, ARG1 drives immunosuppression and metabolic reprogramming but can paradoxically suppress tumorigenesis. Immune modulation via ARG1-polyamine crosstalk regulates T cell differentiation, macrophage polarization, and microbiota interactions, influencing infection and autoimmunity. Endothelial ARG1 exacerbates obesity-related vascular dysfunction, while keratinocyte ARG1 impacts wound healing and psoriasis. Emerging therapies-such as ARG1 inhibitors, engineered extracellular vesicles, and microbiome interventions-show preclinical promise in cancer, cardiovascular, and neurodegenerative diseases. By mapping ARG1's spatiotemporal metabolic networks, this work highlights its dual roles and positions ARG1 as a central player for precision medicine in complex pathologies.

PMID:
41939876
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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