[HTML][HTML] TH2 cells and their cytokines regulate formation and function of lymphatic vessels

K Shin, RP Kataru, HJ Park, BI Kwon, TW Kim… - Nature …, 2015 - nature.com
K Shin, RP Kataru, HJ Park, BI Kwon, TW Kim, YK Hong, SH Lee
Nature communications, 2015nature.com
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 …
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.
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