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TH2 cells and their cytokines regulate formation and function of lymphatic vessels

Author

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  • Kihyuk Shin

    (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology
    Present address: Department of Dermatology, Pusan National University School of Medicine, Busan 609-735, Korea)

  • Raghu P. Kataru

    (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology)

  • Hyeung Ju Park

    (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology)

  • Bo-In Kwon

    (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology)

  • Tae Woo Kim

    (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology)

  • Young Kwon Hong

    (Norris Comprehensive Cancer Center, University of Southern California)

  • Seung-Hyo Lee

    (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology)

Abstract

Lymphatic vessels (LVs) are critical for immune surveillance and involved in the pathogenesis of diverse diseases. LV density is increased during inflammation; however, little is known about how the resolution of LVs is controlled in different inflammatory conditions. Here we show the negative effects of T helper type 2 (TH2) cells and their cytokines on LV formation. IL-4 and IL-13 downregulate essential transcription factors of lymphatic endothelial cells (LECs) and inhibit tube formation. Co-culture of LECs with TH2 cells also inhibits tube formation, but this effect is fully reversed by interleukin (IL)-4 and/or IL-13 neutralization. Furthermore, the in vivo blockade of IL-4 and/or IL-13 in an asthma model not only increases the density but also enhances the function of lung LVs. These results demonstrate an anti-lymphangiogenic function of TH2 cells and their cytokines, suggesting a potential usefulness of IL-4 and/or IL-13 antagonist as therapeutic agents for allergic asthma through expanding LV mediated-enhanced antigen clearance from the inflammatory sites.

Suggested Citation

  • Kihyuk Shin & Raghu P. Kataru & Hyeung Ju Park & Bo-In Kwon & Tae Woo Kim & Young Kwon Hong & Seung-Hyo Lee, 2015. "TH2 cells and their cytokines regulate formation and function of lymphatic vessels," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7196
    DOI: 10.1038/ncomms7196
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