{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T12:14:33Z","timestamp":1793621673066,"version":"4.5.0"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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\u2014including 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\u2014such as ARG1 inhibitors, engineered extracellular vesicles, and microbiome interventions\u2014show preclinical promise in cancer, cardiovascular, and neurodegenerative diseases. By mapping ARG1\u2019s spatiotemporal metabolic networks, this work highlights its dual roles and positions ARG1 as a central player for precision medicine in complex pathologies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1744890","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:48:23Z","timestamp":1773902903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["ARG1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting"],"prefix":"10.3389","volume":"17","author":[{"given":"Lexing","family":"Li","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Wuhan University of Bioengineering","place":["Wuhan, Hubei, China"]},{"name":"National Key Laboratory of Agricultural Microbiology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Wuhan University of Bioengineering","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdie","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Wuhan University of Bioengineering","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Qiu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Wuhan University of Bioengineering","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Wuhan University of Bioengineering","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Wuhan University of Bioengineering","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, and Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University","place":["Bengbu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Wuhan University of Bioengineering","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.3390\/molecules26071990","article-title":"Metformin inhibits the urea cycle and reduces putrescine generation in colorectal cancer cell lines","volume":"26","author":"Zhang","year":"2021","journal-title":"Molecules"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.07.007","article-title":"Arginase overexpression in neurons and its effect on traumatic brain injury","volume":"125","author":"Madan","year":"2018","journal-title":"Mol Genet Metab"},{"key":"B3","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41419-023-06147-7","article-title":"The arginase 1\/ornithine decarboxylase pathway suppresses hdac3 to ameliorate the myeloid cell inflammatory response: implications for retinal ischemic injury","volume":"14","author":"Shosha","year":"2023","journal-title":"Cell Death Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0121727","DOI":"10.1371\/journal.pone.0121727","article-title":"Angiotensin ii-induced arterial thickening, fibrosis and stiffening involves elevated arginase function","volume":"10","author":"Bhatta","year":"2015","journal-title":"PloS One"},{"key":"B5","first-page":"75","article-title":"Augmentation of arginase II Expression in the human endometrial epithelium in the secretory phase","volume":"59","author":"Tajima","year":"2012","journal-title":"J Med Dent Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/bjd\/ljaf057","article-title":"A role for arginase in skin epithelial differentiation and antimicrobial peptide production","volume":"193","author":"Szondi","year":"2025","journal-title":"Br J Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.immuni.2020.06.004","article-title":"Excessive polyamine generation in keratinocytes promotes self-rna sensing by dendritic cells in psoriasis","volume":"53","author":"Lou","year":"2020","journal-title":"Immunity"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13041","article-title":"An arginase-1 snp that protects against the development of pulmonary hypertension in bronchopulmonary dysplasia enhances no-mediated apoptosis in lymphocytes","volume":"4","author":"Trittmann","year":"2016","journal-title":"Physiol Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1129997","article-title":"In-silico studies to recognize repurposing therapeutics toward arginase-I inhibitors as a potential onco-immunomodulators","volume":"14","author":"Zaki","year":"2023","journal-title":"Front Pharmacol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1016\/j.immuni.2024.03.021","article-title":"25-hydroxycholesterol regulates lysosome amp kinase activation and metabolic reprogramming to educate immunosuppressive macrophages","volume":"57","author":"Xiao","year":"2024","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2174\/1566524017666171106114537","article-title":"Vegfr1 signaling regulates il-4-mediated arginase 1 expression in macrophages","volume":"17","author":"Zou","year":"2017","journal-title":"Curr Mol Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176852","article-title":"Cdk8\/19 inhibitor enhances arginase-1 expression in macrophages via stat6 and P38 mapk activation","volume":"979","author":"Mizuno","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI145296","article-title":"Breast cancer-derived gm-csf regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment","volume":"131","author":"Su","year":"2021","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96832","article-title":"Transcription factor fra-1 targets arginase-1 to enhance macrophage-mediated inflammation in arthritis","volume":"129","author":"Hannemann","year":"2019","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41388-023-02884-3","article-title":"Ddr2-regulated arginase activity in ovarian cancer-associated fibroblasts promotes collagen production and tumor progression","volume":"43","author":"Akinjiyan","year":"2024","journal-title":"Oncogene"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114623","article-title":"Mir-135a-5p\/stat6-mediated emt regulates il-4 secretion in non-small cell lung cancer to affect M2-like tam polarization","volume":"155","author":"Gao","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201012-2029OC","article-title":"DNA methylation in the arginase-nitric oxide synthase pathway is associated with exhaled nitric oxide in children with asthma","volume":"184","author":"Breton","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2020.1767373","article-title":"DNA methylation in the promoters of pd-L1, mmp9, arg1, galectin-9, tim-3, vista and tgf-beta genes in hla-dr(-) myeloid cells, compared with hla-dr(+) antigen-presenting cells","volume":"15","author":"Saleh","year":"2020","journal-title":"Epigenetics"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2024.03.003","article-title":"Alkbh5 regulates arginase 1 expression in mdscs and their immunosuppressive activity in tumor-bearing host","volume":"9","author":"Feng","year":"2024","journal-title":"Noncoding RNA Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1128\/MCB.00805-14","article-title":"Cross talk between histone deacetylase 4 and stat6 in the transcriptional regulation of arginase 1 during mouse dendritic cell differentiation","volume":"35","author":"Yang","year":"2015","journal-title":"Mol Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.leukres.2017.12.003","article-title":"Overexpression of arginase 1 is linked to dnmt3a and tet2 mutations in lower-grade myelodysplastic syndromes and chronic myelomonocytic leukemia","volume":"65","author":"Cull","year":"2018","journal-title":"Leuk Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.jhep.2024.05.007","article-title":"Targeting oxct1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via cd8(+) T cells in hepatocellular carcinoma","volume":"81","author":"Zhu","year":"2024","journal-title":"J Hepatol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126923","article-title":"Arginase impedes the resolution of colitis by altering the microbiome and metabolome","volume":"130","author":"Baier","year":"2020","journal-title":"J Clin Invest"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.3390\/cells12081164","article-title":"Timing of interleukin-4 stimulation of macrophages determines their anti-microbial activity during infection with salmonella enterica serovar typhimurium","volume":"12","author":"Brigo","year":"2023","journal-title":"Cells"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e0060824","DOI":"10.1128\/mbio.00608-24","article-title":"Arg1 from cryptococcus neoformans lacks pi3 kinase activity and conveys virulence roles via its ip(3-4) kinase activity","volume":"15","author":"Desmarini","year":"2024","journal-title":"mBio"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-022-02413-8","article-title":"Roles of lncrna lvbu in regulating urea cycle\/polyamine synthesis axis to promote colorectal carcinoma progression","volume":"41","author":"Meng","year":"2022","journal-title":"Oncogene"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113661","article-title":"Vista promotes the metabolism and differentiation of myeloid-derived suppressor cells by stat3 and polyamine-dependent mechanisms","volume":"43","author":"Zhang","year":"2024","journal-title":"Cell Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.04.013","article-title":"Arginase-1 is expressed exclusively by infiltrating myeloid cells in cns injury and disease","volume":"56","author":"Greenhalgh","year":"2016","journal-title":"Brain Behav Immun"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3959-14.2015","article-title":"Sustained arginase 1 expression modulates pathological tau deposits in a mouse model of tauopathy","volume":"35","author":"Hunt","year":"2015","journal-title":"J Neurosci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx164","article-title":"Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1","volume":"113","author":"Bhatta","year":"2017","journal-title":"Cardiovasc Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4186","DOI":"10.1016\/j.cell.2021.06.007","article-title":"Polyamine metabolism is a central determinant of helper T cell lineage fidelity","volume":"184","author":"Puleston","year":"2021","journal-title":"Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq6221","article-title":"Neutralization of net-associated human arg1 enhances cancer immunotherapy","volume":"15","author":"Cane","year":"2023","journal-title":"Sci Transl Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.01.005","article-title":"A relay pathway between arginine and tryptophan metabolism confers immunosuppressive properties on dendritic cells","volume":"46","author":"Mondanelli","year":"2017","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.cmet.2020.01.001","article-title":"Macrophage metabolism of apoptotic cell-derived arginine promotes continual efferocytosis and resolution of injury","volume":"31","author":"Yurdagul","year":"2020","journal-title":"Cell Metab"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80721","article-title":"Arginase 1 is a key driver of immune suppression in pancreatic cancer","volume":"12","author":"Menjivar","year":"2023","journal-title":"Elife"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.703465","article-title":"A novel oral arginase 1\/2 inhibitor enhances the antitumor effect of pd-1 inhibition in murine experimental gliomas by altering the immunosuppressive environment","volume":"11","author":"Pilanc","year":"2021","journal-title":"Front Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0911453","article-title":"Pivotal advance: arginase-1-independent polyamine production stimulates the expression of il-4-induced alternatively activated macrophage markers while inhibiting lps-induced expression of inflammatory genes","volume":"91","author":"Van den Bossche","year":"2012","journal-title":"J Leukoc Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00948","article-title":"Spermine alleviates acute liver injury by inhibiting liver-resident macrophage pro-inflammatory response through atg5-dependent autophagy","volume":"9","author":"Zhou","year":"2018","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0996-7","article-title":"P53 regulation of ammonia metabolism through urea cycle controls polyamine biosynthesis","volume":"567","author":"Li","year":"2019","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"5068","DOI":"10.1016\/j.cell.2023.09.011","article-title":"Arginine reprograms metabolism in liver cancer via rbm39","volume":"186","author":"Mossmann","year":"2023","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2109865","article-title":"The oncogenic role of arg1 in progression and metastasis of hepatocellular carcinoma","volume":"2018","author":"You","year":"2018","journal-title":"BioMed Res Int"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e02402","DOI":"10.1002\/advs.202502402","article-title":"Abnormal beta-hydroxybutyrylation modification of arg1 drives reprogramming of arginine metabolism to promote the progression of colorectal cancer","volume":"12","author":"Lin","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.7150\/thno.26888","article-title":"Arg1 expression defines immunosuppressive subsets of tumor-associated macrophages","volume":"8","author":"Arlauckas","year":"2018","journal-title":"Theranostics"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI153643","article-title":"Annexin A2\/tlr2\/myd88 pathway induces arginase 1 expression in tumor-associated neutrophils","volume":"132","author":"Zhang","year":"2022","journal-title":"J Clin Invest"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1186\/s44280-025-00070-6","article-title":"Arginine as host directed therapy in tuberculosis: insights from modulating arginine metabolism by supplementation and arginase inhibition","volume":"3","author":"Jiang","year":"2025","journal-title":"One Health Adv"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77378","article-title":"Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis","volume":"125","author":"Monin","year":"2015","journal-title":"J Clin Invest"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2021.1956143","article-title":"Inhibition of arginase modulates T-cell response in the tumor microenvironment of lung carcinoma","volume":"10","author":"Sosnowska","year":"2021","journal-title":"Oncoimmunology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmaa116","article-title":"Arg1 functions as a tumor suppressor in breast cancer","volume":"52","author":"Ming","year":"2020","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0280","article-title":"Arginase 1-based immune modulatory vaccines induce anticancer immunity and synergize with anti-pd-1 checkpoint blockade","volume":"9","author":"Aaboe Jorgensen","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111345","article-title":"Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing arginase-1 in rheumatoid arthritis","volume":"127","author":"Zhao","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601330","article-title":"The ap-1 transcription factor C-jun promotes arthritis by regulating cyclooxygenase-2 and arginase-1 expression in macrophages","volume":"198","author":"Hannemann","year":"2017","journal-title":"J Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1042\/CS20200799","article-title":"Myeloid-derived suppressor cells shift th17\/treg ratio and promote systemic lupus erythematosus progression through arginase-1\/mir-322-5p\/tgf-beta pathway","volume":"134","author":"Pang","year":"2020","journal-title":"Clin Sci (Lond)"},{"key":"B53","doi-asserted-by":"publisher","first-page":"331ra40","DOI":"10.1126\/scitranslmed.aae0482","article-title":"Arginase-1-dependent promotion of th17 differentiation and disease progression by mdscs in systemic lupus erythematosus","volume":"8","author":"Wu","year":"2016","journal-title":"Sci Transl Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2174\/0113892010314302240902073112","article-title":"The protective effect of astragalus polysaccharide on experimental autoimmune encephalomyelitis in mice by activating the ampk\/jak\/stat3\/arginase-1 signaling pathway","volume":"26","author":"Wang","year":"2025","journal-title":"Curr Pharm Biotechnol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156379","article-title":"Exploring the therapeutic potential of abelmoschi corolla in psoriasis: mechanisms of action and inflammatory pathway disruption","volume":"138","author":"Qu","year":"2025","journal-title":"Phytomedicine"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/j.jid.2021.09.009","article-title":"An epidermal-specific role for arginase1 during cutaneous wound repair","volume":"142","author":"Crompton","year":"2022","journal-title":"J Invest Dermatol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.06.556606","article-title":"Macrophage-fibroblast crosstalk drives arg1-dependent lung fibrosis via ornithine loading","author":"Yadav","year":"2024","journal-title":"bioRxiv"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948227","article-title":"The role of the complement factor B-arginase-polyamine molecular axis in uremia-induced cardiac remodeling in mice","volume":"50","author":"Yang","year":"2020","journal-title":"Eur J Immunol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1016\/j.cmet.2023.09.010","article-title":"Metabolic support by macrophages sustains colonic epithelial homeostasis","volume":"35","author":"Fritsch","year":"2023","journal-title":"Cell Metab"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-015-2112-0","article-title":"Arginase 1 is a negative regulator of osteoclast differentiation","volume":"48","author":"Yeon","year":"2016","journal-title":"Amino Acids"},{"key":"B61","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.cell.2019.12.002","article-title":"Adrenergic signaling in muscularis macrophages limits infection-induced neuronal loss","volume":"180","author":"Matheis","year":"2020","journal-title":"Cell"},{"key":"B62","doi-asserted-by":"publisher","first-page":"13055","DOI":"10.3390\/ijms232113055","article-title":"Depletion of arg1-positive microglia\/macrophages exacerbates cerebral ischemic damage by facilitating the inflammatory response","volume":"23","author":"Li","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.03.037","article-title":"Changes in L-arginine metabolism by sema4d deficiency induce promotion of microglial proliferation in ischemic cortex","volume":"406","author":"Sawano","year":"2019","journal-title":"Neuroscience"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.131355","article-title":"Stat6\/arg1 promotes microglia\/macrophage efferocytosis and inflammation resolution in stroke mice","volume":"4","author":"Cai","year":"2019","journal-title":"JCI Insight"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.582998","article-title":"Arginase 1 insufficiency precipitates amyloid-beta deposition and hastens behavioral impairment in a mouse model of amyloidosis","volume":"11","author":"Ma","year":"2020","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12974-015-0411-8","article-title":"Arginase 1+ Microglia reduce abeta plaque deposition during il-1beta-dependent neuroinflammation","volume":"12","author":"Cherry","year":"2015","journal-title":"J Neuroinflamm"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01326-3","article-title":"Arg1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain","volume":"26","author":"Stratoulias","year":"2023","journal-title":"Nat Neurosci"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-024-01402-9","article-title":"Luteolin ameliorates chronic stress-induced depressive-like behaviors in mice by promoting the arginase-1(+) microglial phenotype via a ppargamma-dependent mechanism","volume":"46","author":"Yuan","year":"2025","journal-title":"Acta Pharmacol Sin"},{"key":"B69","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s12031-021-01921-8","article-title":"Mir-124 prevents the microglial proinflammatory response by inhibiting the activities of tlr4 and downstream nlrp3 in palmitic acid-treated bv2 cells","volume":"72","author":"Yang","year":"2022","journal-title":"J Mol Neurosci"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114670","article-title":"Osteocalcin-expressing neutrophils from skull bone marrow exert immunosuppressive and neuroprotective effects after tbi","volume":"43","author":"Li","year":"2024","journal-title":"Cell Rep"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12054","article-title":"Increased levels of circulating arginase I in overweight compared to normal weight adolescents","volume":"15","author":"Jung","year":"2014","journal-title":"Pediatr Diabetes"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119588","article-title":"Possible contribution of hepatocyte secretion to the elevation of plasma exosomal arginase-1 in high-fat diet-fed mice","volume":"278","author":"Ogino","year":"2021","journal-title":"Life Sci"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2011.09.012","article-title":"Arginase I and the very low-density lipoprotein receptor are associated with phenotypic biomarkers for obesity","volume":"28","author":"Kim","year":"2012","journal-title":"Nutrition"},{"key":"B74","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s13105-017-0597-6","article-title":"Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and L-arginine metabolism in mice","volume":"74","author":"Ito","year":"2018","journal-title":"J Physiol Biochem"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2022.130263","article-title":"Pathophysiological correlation of arginase-1 in development of type 2 diabetes from obesity in adolescents","volume":"1867","author":"Mazrouei","year":"2023","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"B76","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1124\/jpet.115.224592","article-title":"A novel arginase inhibitor derived from scutellavia indica restored endothelial function in apoe-null mice fed a high-cholesterol diet","volume":"355","author":"Hwang","year":"2015","journal-title":"J Pharmacol Exp Ther"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-111014","article-title":"Arginase inhibitor 2,3,5,4\u2019-tetrahydroxystilbene-2-O-beta-D-glucoside activates endothelial nitric oxide synthase and improves vascular function","volume":"83","author":"Yi","year":"2017","journal-title":"Planta Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-011-0841-2","article-title":"S-nitrosation of arginase 1 requires direct interaction with inducible nitric oxide synthase","volume":"355","author":"Dunn","year":"2011","journal-title":"Mol Cell Biochem"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.07.083","article-title":"Arginase inhibition restores endothelial function in diet-induced obesity","volume":"451","author":"Chung","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00219","article-title":"Arginase 1 mediates increased blood pressure and contributes to vascular endothelial dysfunction in deoxycorticosterone acetate-salt hypertension","volume":"4","author":"Toque","year":"2013","journal-title":"Front Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00529.2016","article-title":"Obesity-induced vascular inflammation involves elevated arginase activity","volume":"313","author":"Yao","year":"2017","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.052","article-title":"Erythrocytes from patients with type 2 diabetes induce endothelial dysfunction via arginase I","volume":"72","author":"Zhou","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"2890","DOI":"10.3390\/cells11182890","article-title":"Systemic administration of pegylated arginase-1 attenuates the progression of diabetic retinopathy","volume":"11","author":"Abdelrahman","year":"2022","journal-title":"Cells"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht329","article-title":"Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation","volume":"35","author":"Wang","year":"2014","journal-title":"Eur Heart J"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.318338","article-title":"Arginase-1 deletion in erythrocytes promotes vascular calcification via enhanced gsnor (S-nitrosoglutathione reductase) expression and no signaling in smooth muscle cells","volume":"42","author":"Gogiraju","year":"2022","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"e103048","DOI":"10.1371\/journal.pone.0103048","article-title":"Arginase inhibition ameliorates hepatic metabolic abnormalities in obese mice","volume":"9","author":"Moon","year":"2014","journal-title":"PloS One"},{"key":"B87","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1080\/17520363.2025.2455924","article-title":"Arginase 1 genetic variation is associated with the risk of vascular complications in type 2 diabetes","volume":"19","author":"Chen","year":"2025","journal-title":"biomark Med"},{"key":"B88","doi-asserted-by":"publisher","first-page":"508","DOI":"10.3390\/cells11030508","article-title":"Physical interaction between embryonic stem cell-expressed ras (Eras) and arginase-1 in quiescent hepatic stellate cells","volume":"11","author":"Pudewell","year":"2022","journal-title":"Cells"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-022-03318-3","article-title":"Decreased arg1 expression as an adverse prognostic phenotype in non-alcoholic non-virus-related hepatocellular carcinoma","volume":"481","author":"Shigematsu","year":"2022","journal-title":"Virchows Arch"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018010074","article-title":"Interactions between macrophages and cyst-lining epithelial cells promote kidney cyst growth in pkd1-deficient mice","volume":"29","author":"Yang","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167083","article-title":"Spermidine ameliorates osteoarthritis via altering macrophage polarization","volume":"1870","author":"Ou","year":"2024","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00458-17","article-title":"Utilization of host polyamines in alternatively activated macrophages promotes chronic infection by brucella abortus","volume":"86","author":"Kerrinnes","year":"2018","journal-title":"Infect Immun"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.3390\/v13071236","article-title":"Proteome analysis in pam cells reveals that african swine fever virus can regulate the level of intracellular polyamines to facilitate its own replication through arg1","volume":"13","author":"Ai","year":"2021","journal-title":"Viruses"},{"key":"B94","doi-asserted-by":"publisher","first-page":"e0283696","DOI":"10.1371\/journal.pone.0283696","article-title":"Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing leishmania amazonensis infection","volume":"18","author":"Zanatta","year":"2023","journal-title":"PloS One"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2024.108863","article-title":"Expression pattern of arg1 and inos genes in macrophages of rhombomys opimus, balb\/C and C57bl\/6 mice exposed to leishmania major and salivary gland homogenates of phlebotomus papatasi","volume":"267","author":"Shirazian","year":"2024","journal-title":"Exp Parasitol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.3390\/cells10071823","article-title":"Cytokine-mediated regulation of arg1 in macrophages and its impact on the control of salmonella enterica serovar typhimurium infection","volume":"10","author":"Brigo","year":"2021","journal-title":"Cells"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154874","article-title":"3, 3\u2019-diindolylmethane enhances macrophage efferocytosis and subsequently relieves visceral pain via the ahr\/nrf2\/arg-1-mediated arginine metabolism pathway","volume":"116","author":"Yang","year":"2023","journal-title":"Phytomedicine"},{"key":"B98","doi-asserted-by":"publisher","first-page":"e1002417","DOI":"10.1371\/journal.ppat.1002417","article-title":"Progressive visceral leishmaniasis is driven by dominant parasite-induced stat6 activation and stat6-dependent host arginase 1 expression","volume":"8","author":"Osorio","year":"2012","journal-title":"PloS Pathog"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1016\/j.immuni.2023.07.014","article-title":"Loss of cd4(+) T cell-intrinsic arginase 1 accelerates th1 response kinetics and reduces lung pathology during influenza infection","volume":"56","author":"West","year":"2023","journal-title":"Immunity"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1601423","article-title":"Fusobacterium-associated molecular and immunological alterations in colorectal cancer: insights from a norwegian cohort","volume":"16","author":"Omran","year":"2025","journal-title":"Front Immunol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1186\/s40001-023-01257-6","article-title":"Resveratrol alleviates dss-induced ibd in mice by regulating the intestinal microbiota-macrophage-arginine metabolism axis","volume":"28","author":"Xu","year":"2023","journal-title":"Eur J Med Res"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-22-0721","article-title":"Arginase 1\/2 inhibitor oatd-02: from discovery to first-in-man setup in cancer immunotherapy","volume":"22","author":"Borek","year":"2023","journal-title":"Mol Cancer Ther"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00931","article-title":"Discovery of N-substituted 3-amino-4-(3-boronopropyl)Pyrrolidine-3-carboxylic acids as highly potent third-generation inhibitors of human arginase I and ii","volume":"62","author":"Van Zandt","year":"2019","journal-title":"J Med Chem"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.116033","article-title":"Novel orally bioavailable piperidine derivatives as extracellular arginase inhibitors developed by a ring expansion","volume":"264","author":"Gzik","year":"2024","journal-title":"Eur J Med Chem"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2024.106959","article-title":"Liposomal nomega-hydroxy-L-norarginine, a proof-of-concept: arginase inhibitors can be incorporated in liposomes while retaining their therapeutic activity ex vivo","volume":"204","author":"Markova","year":"2025","journal-title":"Eur J Pharm Sci"},{"key":"B106","doi-asserted-by":"publisher","first-page":"e2410067","DOI":"10.1002\/advs.202410067","article-title":"Engineered mesenchymal stem cell-derived extracellular vesicles scavenge self-antigens for psoriasis therapy via modulating metabolic and immunological disorders","volume":"12","author":"Zhou","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009930","article-title":"Arginase-1-specific T cells target and modulate tumor-associated macrophages","volume":"13","author":"Martinenaite","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01993","article-title":"Examining arginase-1 trimerization uncovers a promising allosteric site for inhibition","volume":"68","author":"Dechenne","year":"2025","journal-title":"J Med Chem"},{"key":"B109","doi-asserted-by":"publisher","first-page":"3990","DOI":"10.3390\/ijms21113990","article-title":"Arginase-1+ Exosomes from reprogrammed macrophages promote glioblastoma progression","volume":"21","author":"Azambuja","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2015.1056945","article-title":"Elevated arg1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients","volume":"16","author":"Jung","year":"2015","journal-title":"Cancer Biol Ther"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2025.108227","article-title":"Predictive efficacy of plasma arginase 1 as a novel biomarker for mechanical ventilated patients with sepsis induced acute respiratory distress syndrome: A prospective cohort study","volume":"246","author":"Charoensappakit","year":"2025","journal-title":"Respir Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1744890\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:48:25Z","timestamp":1773902905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1744890\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":111,"alternative-id":["10.3389\/fimmu.2026.1744890"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1744890","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]},"article-number":"1744890"}}