title: Conditional ablation of LYVE-1+ cells unveils defensive roles of lymphatic vessels in intestine and lymph nodes.
abstract: To unveil the organotypic role and vulnerability of lymphatic vessels, we generated a lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-Cre/iDTR double-transgenic mouse and ablated LYVE-1-expressing lymphatic vessels in adult mice in a diphtheria toxin (DT)-inducible manner based on selective expression of LYVE-1 in most lymphatic vessels. Strikingly, lymphatic vessels in the small intestine and lymph nodes were rapidly ablated, but lymphatic vessels in the other organs were relatively intact at 24 hours after DT administration. Unexpectedly, LYVE-1-Cre/iDTR mice died of sepsis without visible edema at 24 and 60 hours after DT administration. The cause of death appeared to be related to acute failure of immune surveillance systems in the small intestine and draining lymph nodes. Of note, acute loss of lymphatic lacteals in intestinal villi appeared to trigger distortion of blood capillaries and the whole architecture of the villi, whereas acute loss of lymphatic vessels in lymph nodes caused dysfunction of lymph drainage and abnormal distribution of dendritic cells and macrophages. Thus, intact lymphatic vessels are required for structural and functional maintenance of surrounding tissues in an organotypic manner, at least in the intestine and lymph nodes.
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea;
authors.forename: Jeon Yeob
authors.initials: JY
authors.lastname: Jang
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Koh
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Junyeop
authors.initials: J
authors.lastname: Lee
authors.forename: Kyoo Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Ook Joon
authors.initials: OJ
authors.lastname: Yoo
mesh_terms: D000818:Animals; D006023:Glycoproteins / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D042601:Lymphatic Vessels; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D006023:Glycoproteins; D026901:Membrane Transport Proteins; C492273:LYVE1 protein, mouse