title: TH2 cells and their cytokines regulate formation and function of lymphatic vessels.
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.
authors: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors: Kihyuk
authors: K
authors: Shin
authors: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors: Raghu P
authors: RP
authors: Kataru
authors: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors: Hyeung Ju
authors: HJ
authors: Park
authors: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors: Bo-In
authors: BI
authors: Kwon
authors: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors: Tae Woo
authors: TW
authors: Kim
authors: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.
authors: Young Kwon
authors: YK
authors: Hong
authors: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors: Seung-Hyo
authors: SH
authors: Lee
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000946:Antigens, Fungal; D001236:Aspergillus oryzae / Q000737:chemistry / Q000276:immunology; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D042583:Lymphangiogenesis / Q000235:genetics / Q000276:immunology*; D042601:Lymphatic Vessels / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology; D000098551:Prospero-Related Homeobox 1 Protein; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D057134:Antibodies, Neutralizing; D000946:Antigens, Fungal; D006023:Glycoproteins; D018398:Homeodomain Proteins; D018793:Interleukin-13; D015847:Interleukin-4; D026901:Membrane Transport Proteins; D010047:Ovalbumin; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit; C492273:LYVE1 protein, mouse