Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner

Chemokines and adhesion molecules up-regulated in lymphatic endothelial cells (LECs) during tissue inflammation are thought to enhance dendritic cell (DC) migration to draining lymph nodes, but the in vivo control of this process is not well understood. We performed a transcriptional profiling analy...

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Published in:	Blood Vol. 118; no. 1; pp. 205 - 215
Main Authors:	Vigl, Benjamin, Aebischer, David, Nitschké, Maximilian, Iolyeva, Maria, Röthlin, Tamara, Antsiferova, Olga, Halin, Cornelia
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 07-07-2011 Americain Society of Hematology
Subjects:	Animals Biological and medical sciences Cell Movement - immunology Chemokine CCL21 - genetics Chemokine CCL21 - immunology Chemokine CCL21 - metabolism Dendritic Cells - cytology Dendritic Cells - immunology Dermatitis, Contact - immunology Ear, External - immunology Endothelial Cells - immunology Female Gene Expression - immunology Gene Expression Profiling Hematologic and hematopoietic diseases Intercellular Adhesion Molecule-1 - genetics Intercellular Adhesion Molecule-1 - immunology Intercellular Adhesion Molecule-1 - metabolism Lymph Nodes - cytology Lymph Nodes - immunology Medical sciences Mice Mice, Inbred C57BL Mice, Mutant Strains Oligonucleotide Array Sequence Analysis Receptors, CCR7 - genetics Receptors, CCR7 - immunology Receptors, CCR7 - metabolism Up-Regulation - immunology Vascular Cell Adhesion Molecule-1 - genetics Vascular Cell Adhesion Molecule-1 - immunology Vascular Cell Adhesion Molecule-1 - metabolism Dendritic cell Cell motility Endothelial cell Lymphatic system Hematology Antigen presenting cell Lymphatic Inflammation Gene expression Cell migration Endothelium
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Summary:	Chemokines and adhesion molecules up-regulated in lymphatic endothelial cells (LECs) during tissue inflammation are thought to enhance dendritic cell (DC) migration to draining lymph nodes, but the in vivo control of this process is not well understood. We performed a transcriptional profiling analysis of LECs isolated from murine skin and found that inflammation induced by a contact hypersensitivity (CHS) response up-regulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines. Importantly, the lymphatic markers Prox-1, VEGFR3, and LYVE-1 were significantly down-regulated during CHS. By contrast, skin inflammation induced by complete Freund adjuvant induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. Fluorescein isothiocyanate painting experiments revealed that DC migration to draining lymph nodes was more strongly increased in complete Freund adjuvant-induced than in CHS-induced inflammation. Surprisingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 protein in LECs. Although the requirement for CCR7 signaling became further pronounced during inflammation, CCR7-independent signals had an additional, albeit moderate, impact on enhancing DC migration. Collectively, these findings indicate that DC migration in response to inflammation is stimulus-specific, mainly CCR7-dependent, and overall only moderately enhanced by LEC-induced genes other than CCL21.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood-2010-12-326447