Th2 cells and their cytokines regulate formation and function of lymphatic vessels
In this study, the roles of Th2 cells and their cytokines, IL-4 and IL-13 in lymphangiogenesis were investigated using an in vitro lymphatic endothelial cell (LEC) culture system and an allergic asthma model. Th2 cells were demonstrated to have anti-lymphangiogenic effects that are dependent on IL-4 and/or IL-13 mediated signaling. Furthermore, blockade of IL-4 and/or IL-13 increased lymphatic vessel (LV) density and function, as well as antigen clearance from lungs and airways of allergen-induced asthmatic mice. In summary, it was demonstrated that not only lymph nodes but also lung and trachea lymphangiogenesis are regulated by Th2 cells and their cytokines, IL-4 and IL-13 in an allergic asthma model.
LVs are critical for immune surveillance and involved in the pathogenesis of a diverse number of diseases. The density of LVs is increased during inflammation; however little is known about how resolution of LVs is controlled in different inflammatory conditions. In this study, we investigated the effects of Th2 cells and their cytokines on the formation of LVs by using an in vitro LEC culture system and an in vivo allergic asthma model.
We showed that IL-4 and IL-13 down-regulated essential transcription factors of LECs, and inhibited tube formation. Co-cultures of LECs with Th2 cells also inhibited tube formation, but this effect was fully reversed by neutralization of IL-4 and IL-13. Furthermore, an in vivo blockade of IL-4 and IL-13 in an allergic asthma model not only increased the density but also enhanced the function of lung LVs.
In conclusion, these results demonstrated a novel anti-lymphangiogenic function of Th2 cells and their cytokines, suggesting a potential usefulness of IL-4 and/or IL-13 antagonists as therapeutic agents for allergic asthma through additional mechanisms by which expanding LVs mediated rapid clearance of antigens from inflammatory sites.
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Shin K. et al. Nature Communications, 2015, 6:6196, doi: 10.1038/ncomms7196
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