The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Th2 Cytokines Inhibit Lymphangiogenesis
Open accessAbstract
Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC) proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2) cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4) and interleukin-13 (IL-13) have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.
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“the Th2 cytokines IL-4 and IL-13 are linked to reduced LEC viability and LEC gene expression (143).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [143]
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Self-citationCD4+ cells regulate fibrosis and lymphangiogenesis in response to lymphatic fluid stasis
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Scar Acceleration Method—MAC® in the Treatment of Chronic Wounds in Lymphedema: Case Report
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(2024) · Haug Verlag in Georg Thieme Verlag KG eBooks · doi:10.1055/b-0044-201934
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Mechanisms and treatments of lymphedema
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Self-citationHao, Y., Zhang, Y., Zong, J., Wu, G., Wang, Y., Wang, Y., & Wang, Y. (2026) · International Journal of Obesity · doi:10.1038/s41366-026-02178-0
Association between autoimmune diseases and risk of developing breast cancer-related lymphedema
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Metadata
- Authors
- Savetsky, I. L., Ghanta, S., Gardenier, J. C., Torrisi, J. S., García Nores, G. D., Hespe, G. E., Nitti, M. D., Kataru, R. P., & Mehrara, B. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Mehrara, Babak J.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-06-03
- Volume
- 10
- Issue
- 6
- Pages
- e0126908
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4454507
- OpenAlex
- W560736474
- Cited by
- 114
- References
- 23
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 11 · 2023: 6 · 2022: 18 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 12 · 2016: 6 · 2015: 2
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748)
- National Heart, Lung, and Blood Institute (R01HL111130)
- National Cancer Institute (T32CA009685, P30CA008748, T32CA009501)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
- Keywords
- lymphangiogenesis, Th2 cytokines, IL-4, IL-13, lymphatic endothelial cells, lymphedema, anti-lymphangiogenic therapy, lymphatic fibrosis, extracellular matrix, monoclonal antibodies
- MeSH terms
- Animals, Cell Movement, Cell Survival, Male, Interleukin-4, Th2 Cells, Interleukin-13, Lymphangiogenesis, Endothelial Cells, Cell Proliferation, Mice
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