| Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. | |
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MedLine Citation:
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PMID: 19734211 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the paracortex of the lymph node (LN), T zone fibroblastic reticular cells (TRCs) orchestrate an immune response by guiding lymphocyte migration both physically, by creating three-dimensional (3D) cell networks, and chemically, by secreting the chemokines CCL19 and CCL21 that direct interactions between CCR7-expressing cells, including mature dendritic cells and naive T cells. TRCs also enwrap matrix-based conduits that transport fluid from the subcapsular sinus to high endothelial venules, and fluid flow through the draining LN rapidly increases upon tissue injury or inflammation. To determine whether fluid flow affects TRC organization or function within a 3D network, we regenerated the 3D LN T zone stromal network by culturing murine TRC clones within a macroporous polyurethane scaffold containing type I collagen and Matrigel and applying slow interstitial flow (1-23 microm/min). We show that the 3D environment and slow interstitial flow are important regulators of TRC morphology, organization, and CCL21 secretion. Without flow, CCL21 expression could not be detected. Furthermore, when flow through the LN was blocked in mice in vivo, CCL21 gene expression was down-regulated within 2 h. These results highlight the importance of lymph flow as a homeostatic regulator of constitutive TRC activity and introduce the concept that increased lymph flow may act as an early inflammatory cue to enhance CCL21 expression by TRCs, thereby ensuring efficient immune cell trafficking, lymph sampling, and immune response induction. |
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Authors:
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Alice A Tomei; Stefanie Siegert; Mirjam R Britschgi; Sanjiv A Luther; Melody A Swartz |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-04 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 183 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-21 Completed Date: 2009-11-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 4273-83 Citation Subset: AIM; IM |
Affiliation:
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Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation / immunology Chemokine CCL21 / biosynthesis*, genetics Clone Cells Fibroblasts / cytology, immunology, metabolism Immunity, Innate Immunophenotyping Lymph / cytology, immunology*, metabolism Lymph Nodes / cytology*, immunology*, metabolism Mice Mice, Knockout Models, Immunological Organ Culture Techniques Stromal Cells / cytology, immunology, metabolism Tissue Engineering* / methods Transduction, Genetic / methods |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL21 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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