Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema Journal Article

Authors: Avraham, T.; Zampell, J. C.; Yan, A.; Elhadad, S.; Weitman, E. S.; Rockson, S. G.; Bromberg, J.; Mehrara, B. J.
Article Title: Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema
Abstract: Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4+ T-cell inflammation and T-helper 2 (Th2) differentiation. Using mice deficient in T cells or CD4+ cells, we show that this inflammatory response is necessary for the pathological changes of lymphedema, including fibrosis, adipose deposition, and lymphatic dysfunction. Further, we show that inhibition of Th2 differentiation using interleukin-4 (IL-4) or IL-13 blockade prevents initiation and progression of lymphedema by decreasing tissue fibrosis and significantly improving lymphatic function, independent of lymphangiogenic growth factors. We show that CD4 + inflammation is a critical regulator of tissue fibrosis and lymphatic dysfunction in lymphedema and that inhibition of Th2 differentiation markedly improves lymphatic function independent of lymphangiogenic cytokine expression. Notably, preventing and/or reversing the development of pathological tissue changes that occur in lymphedema may be a viable treatment strategy for this disorder. © FASEB.
Keywords: inflammation; lymphangiogenesis; lymphatic endothelial cell
Journal Title: FASEB Journal
Volume: 27
Issue: 3
ISSN: 0892-6638
Publisher: Federation of American Societies for Experimental Biology  
Date Published: 2013-03-01
Start Page: 1114
End Page: 1126
Language: English
DOI: 10.1096/fj.12-222695
PROVIDER: scopus
PMCID: PMC3574290
PUBMED: 23193171
Notes: --- - "Export Date: 1 April 2013" - "CODEN: FAJOE" - "Source: Scopus"
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MSK Authors
  1. Jacqueline Bromberg
    105 Bromberg
  2. Sonia Elhadad
    10 Elhadad
  3. Babak Mehrara
    257 Mehrara
  4. Tomer Avraham
    33 Avraham
  5. Jamie Christine Zampell
    29 Zampell
  6. Alan Yan
    20 Yan
  7. Evan Scott Weitman
    18 Weitman