Fluid Flow Regulates Stromal Cell Organization and CCL21 Expression in a Tissue-Engineered Lymph Node Microenvironment

被引:116
作者
Tomei, Alice A.
Siegert, Stefanie [2 ]
Britschgi, Mirjam R. [2 ]
Luther, Sanjiv A. [2 ]
Swartz, Melody A. [1 ]
机构
[1] Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lab Mechanobiol & Morphol, CH-1015 Lausanne, Switzerland
[2] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland
基金
瑞士国家科学基金会;
关键词
FIBROBLASTIC RETICULAR CELLS; HIGH ENDOTHELIAL VENULES; IN-VITRO; INTERSTITIAL FLOW; CONDUIT SYSTEM; CHEMOKINE EXPRESSION; EXTRACELLULAR-MATRIX; COLLAGEN CULTURES; DENDRITIC CELLS; T-CELLS;
D O I
10.4049/jimmunol.0900835
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 mu m/min). We show that the 3D environment and slow interstitial How 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. The Journal of Immunology, 2009, 183: 4273-4283.
引用
收藏
页码:4273 / 4283
页数:11
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