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Series GSE6257 Query DataSets for GSE6257
Status Public on Dec 05, 2006
Title An inflammation-induced mechanism for leukocyte transmigration of lymphatic vessel endothelium.
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Summary The exit of antigen-presenting cells (APC) and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels is however unknown. Here we show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LEC) leading to expression of the key leukocyte adhesion receptors ICAM-1, VCAM-1 and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of DC via afferent lymphatics. Lastly, we show that TNF_-stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking mAbs. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for anti-inflammatory therapy.
Keywords: TNFalpha, Lymphatic endothelium, induction, Inflammation
 
Overall design Global gene expression profile of normal dermal lymphatic endothelial cells cultured in media alone (no TNF) compared to that of normal dermal lymphatic endothelial cells stimulated with TNFalpha, 1 ng/ml for 48h.Triplicate biological samples were analyzed from human lymphatic endothelial cells (3 x controls; 3 x TNF treated) and a single sample analyzed from mouse lymphatic endothelial cells (1 x controls; 1 x TNF treated).
 
Contributor(s) Johnson L, Clasper S, Holt A, Lalor P, Baban D, Jackson DG
Citation(s) 17116732
Submission date Nov 09, 2006
Last update date Mar 25, 2019
Contact name Dilair Baban
E-mail(s) dilair.baban@well.ox.ac.uk
Phone +44(0)1865287521
Organization name University of Oxford
Department Wellcome Trust Centre Human Genetics
Lab Genomics
Street address Roosevelt Drive
City Oxford
ZIP/Postal code OX3 7BN
Country United Kingdom
 
Platforms (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (8)
GSM143704 Mouse lymphatic endothelial cells Control
GSM143705 Mouse lymphatic endothelial cells TNFa treated
GSM143717 Human lymphatic endothelial cells Control_Rep 1
Relations
BioProject PRJNA100539

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Supplementary file Size Download File type/resource
GSE6257_RAW.tar 60.2 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file

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