Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. Export

@article{citeulike:5879375, abstract = {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.}, author = {Tomei, Alice A. and Siegert, Stefanie and Britschgi, Mirjam R. and Luther, Sanjiv A. and Swartz, Melody A.}, citeulike-article-id = {5879375}, citeulike-linkout-0 = {http://dx.doi.org/10.4049/jimmunol.0900835}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19734211}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19734211}, day = {1}, doi = {10.4049/jimmunol.0900835}, issn = {1550-6606}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, keywords = {chemokine, lymph, lymph\_node}, month = {October}, number = {7}, pages = {4273--4283}, posted-at = {2009-10-02 19:25:43}, priority = {2}, title = {Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment.}, url = {http://dx.doi.org/10.4049/jimmunol.0900835}, volume = {183}, year = {2009} }

TY - JOUR ID - citeulike:5879375 L3 - citeulike-article-id:5879375 N2 - 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. IS - 7 JF - Journal of immunology (Baltimore, Md. : 1950) SN - 1550-6606 EP - 4283 TI - Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. VL - 183 SP - 4273 KW - chemokine KW - lymph KW - lymph_node AU - Tomei, Alice AU - Siegert, Stefanie AU - Britschgi, Mirjam AU - Luther, Sanjiv AU - Swartz, Melody PY - 2009/10/01/ UR - http://dx.doi.org/10.4049/jimmunol.0900835 ER -