ArticleAmerican journal of respiratory cell and molecular biology2015
Lung Angiogenesis Requires CD4(+) Forkhead Homeobox Protein-3(+) Regulatory T Cells.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- CNS1-dependent regulatory T cells shape recovery from acute lung injury.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma.Oncoimmunology · 2025Article
- Microenvironmental regulation and remodeling of breast cancer angiogenesis: from basic mechanisms to clinical therapeutic implications.Discover oncology · 2025Review
- T Regulatory Mechanisms in Airway and Interstitial Lung Disease.Seminars in respiratory and critical care medicine · 2025Review
- Role of Peripheral Blood Regulatory T Cells and IL-2 in the Collateral Circulation of Acute Ischemic Stroke.International journal of general medicine · 2025Article
- Revisiting Tregs in cancer and beyond: immunological control and therapeutic potential.Frontiers in immunology · 2025Review
- Toll-like receptor 2 deficiency exacerbates corneal angiogenesis in injury by impairing regulatory T cells.Theranostics · 2025Article
- The dual role of tissue regulatory T cells in tissue repair: return to homeostasis or fibrosis.Frontiers in immunology · 2025Review
- Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke.Journal of neuroinflammation · 2024Review
- Role of regulatory T cells in mouse lung development.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Regulatory T cells in lung disease and transplantation.Bioscience reports · 2023Review
- Differential roles of regulatory T cells in acute respiratory infections.The Journal of clinical investigation · 2023Review
- The microsomal prostaglandin E synthase-1/prostaglandin E2 axis induces recovery from ischaemia via recruitment of regulatory T cells.Cardiovascular research · 2023Article
- Regulatory T cell and macrophage crosstalk in acute lung injury: future perspectives.Cell death discovery · 2023Review
- Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.International journal of molecular sciences · 2022Article
- Stromal Vascular Fraction Reverses the Age-Related Impairment in Revascularization following Injury.Journal of vascular research · 2022Article
- Article
- Regulatory T Cells in Angiogenesis.Journal of immunology (Baltimore, Md. : 1950) · 2020Review
- Delayed Akt suppression in the lipopolysaccharide-induced acute lung injury promotes resolution that is associated with enhanced effector regulatory T cells.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Reparative T lymphocytes in organ injury.The Journal of clinical investigation · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Angiogenesis in ischemic organs is modulated by immune cells. Systemic neovascularization of the ischemic lung requires macrophages, with chemokines playing a central role in new vessel growth. Because regulatory T (Treg) cells modulate tumor-induced neovascularization, we questioned whether this CD4(+) lymphocyte subset impacts blood vessel growth during ischemia. In a model of left lung ischemia, an increase in CD4(+) CD25(+) forkhead homeobox protein-3 (Foxp3)(+) cells was observed 3-5 days after the onset of ischemia in wild-type C57Bl/6 mice. Using transgenic mice where Foxp3(+) Treg cells can be depleted with diphtheria toxin (DT; Foxp3(DTR)), we unexpectedly found that Foxp3(+) Treg depletion led to markedly reduced lung angiogenesis (90% reduction from Foxp3(gfp) controls). Adoptive transfer studies using CD4(+) CD25(+) splenocytes from congenic CD45.1 mice into Foxp3(+) Treg-depleted mice showed an almost complete recovery of the angiogenic phenotype (80% of Foxp3(gfp) controls). A survey of lung gene expression of angiogenic (lipopolysaccharide-induced CXC chemokine [LIX], IL-6, IL-17) and angiostatic (IFN-γ, transforming growth factor-β, IL-10) cytokines showed Treg-dependent differences only in LIX (CXCL5) and IL-6. Protein confirmation demonstrated a significant reduction in LIX in Treg-deficient mice compared with controls 5 days after the onset of ischemia. Phenotyping other inflammatory cells in the lung by multicolor flow cytometry demonstrated a significantly reduced number of macrophages (major histocombatibility complex class II [MHCII](int), CD11C(+)) in Treg-deficient lungs compared with Treg-sufficient lungs. Treg cells are essential for maximal systemic angiogenesis after pulmonary ischemia. One likely mechanism responsible for the decrease in angiogenesis in Treg-depleted mice was the decline in the essential CXC chemokine, LIX.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.