ArticleTranslational research : the journal of laboratory and clinical medicine2019
T helper 2 differentiation is necessary for development of lymphedema.
Article in Translational research : the journal of laboratory and clinical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Keratinocytes: A key player in skin immunity and their emerging roles in secondary lymphedema.JID innovations : skin science from molecules to population health · 2026Review
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Advances in molecular innate immune regulation in the development and therapeutic strategies of allergic rhinitis vaccines.Frontiers in immunology · 2026Review
- Inhibition of Th2 Differentiation Accelerates Chronic Wound Healing by Facilitating Lymphangiogenesis.Biomedicines · 2025Article
- Lymphedema pathogenesis involves antigen-driven expansion of CD4+ T cells in skin.Frontiers in immunology · 2025Article
- Breast Cancer-Related Lymphedema Results in Impaired Epidermal Differentiation and Tight Junction Dysfunction.The Journal of investigative dermatology · 2025Article
- Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3Nature communications · 2024Article
- The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.Journal of neuroinflammation · 2024Observational
- [Research advances on stem cell-based treatments in animal studies and clinical trials of lymphedema].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Article
- Role of inducible nitric oxide (iNOS) and nitrosative stress in regulating sex differences in secondary lymphedema.Frontiers in physiology · 2024Article
- Increased infiltration of CD4BMC immunology · 2023Article
- Abnormal Lymphatic Sphingosine-1-Phosphate Signaling Aggravates Lymphatic Dysfunction and Tissue Inflammation.Circulation · 2023Article
- Analysis of CD4Gland surgery · 2023Article
- The emerging importance of lymphatics in health and disease: an NIH workshop report.The Journal of clinical investigation · 2023Review
- Abnormal lymphatic S1P signaling aggravates lymphatic dysfunction and tissue inflammation.medRxiv : the preprint server for health sciences · 2023Article
- Lymphatic Vascular Permeability.Cold Spring Harbor perspectives in medicine · 2022Review
- Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema.International journal of molecular sciences · 2022Review
- TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation.Clinical and translational medicine · 2022Article
- Hypoxia and Hypoxia-Inducible Factors in Lymphedema.Frontiers in pharmacology · 2022Review
- Pharmacological Treatment of Secondary Lymphedema.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
T cells infiltrating lymphedematous tissues have a mixed T helper 1 (Th1) and Th2 differentiation profile. Treatment with neutralizing antibodies targeting cytokines that promote Th2 differentiation (interleukin 4 [IL-4] and IL-13) decreases the severity of lymphedema in preclinical models, suggesting that Th2 cells play a key role in the pathology of this disease. However, these previous studies do not address the contribution of Th1 cells and it remains unknown if IL-4 and IL-3 blockade acts primarily on T cells or decreases the pathological changes of lymphedema by other mechanisms. Therefore, this study sought to analyze the effect of lymphatic injury in transgenic mice with mutations that cause defects in Th1 and Th2 cell generation (T-bet knockout or T-betKO and STAT6 knockout or STAT6KO mice, respectively). Using both the mouse tail and popliteal lymph node dissection models of lymphedema, we show that Th2-deficient (STAT6KO) mice are protected from developing lymphedema, have decreased fibrosis, increased collateral vessel formation, and preserved collecting lymphatic vessel pumping function. In contrast, mice with defective Th1 cell generation (T-betKO) develop disease with the same severity as wild-type controls. Taken together, our results suggest that Th2 differentiation is necessary for development of lymphedema following lymphatic injury and that Th1 differentiation does not significantly contribute to the pathology of the disease. Such findings are important as immunotherapy directed at Th2 cells has been found to be effective in well-studied Th2-mediated diseases such as asthma and atopic dermatitis and may therefore be similarly useful for lymphedema management.
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