1. IL-7-producing stromal cells are critical for lymph node remodeling
- Author
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Jürgen Westermann, Priyanka Narang, Burkhard Ludewig, Kerim Hoorweg, Tom Cupedo, Lucas Onder, Cornelia Halin, Maria Iolyeva, Qian Chai, Mark Coles, Elke Scandella, Ellen R. Richie, Paul M. Kaye, and Hematology
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Stromal cell ,medicine.medical_treatment ,Immunology ,Plenary Paper ,Gene Expression ,Mice, Transgenic ,Biology ,Lymphocytic Choriomeningitis ,Kidney ,Biochemistry ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Reticular cell ,Lymphocyte homeostasis ,medicine ,Lymph node stromal cell ,Animals ,Humans ,Lymph node ,Cells, Cultured ,030304 developmental biology ,Cell Proliferation ,Lymphatic Vessels ,0303 health sciences ,Microscopy, Confocal ,Reverse Transcriptase Polymerase Chain Reaction ,Interleukin-7 ,Endothelial Cells ,Cell Biology ,Hematology ,Fibroblasts ,Fluid transport ,Immunohistochemistry ,Cell biology ,Mice, Inbred C57BL ,Luminescent Proteins ,medicine.anatomical_structure ,Lymphatic system ,Cytokine ,Female ,Lymph Nodes ,Stromal Cells ,030215 immunology - Abstract
Nonhematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures, such as lymph node (LN) trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. IL-7 is an important stromal cell-derived cytokine that has been considered to be derived mainly from T-cell zone fibroblastic reticular cells. We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7 both in human and murine LNs. Using bacterial artificial chromosome transgenic IL-7–Cre mice, we found that fibroblastic reticular cells and LECs strongly up-regulated IL-7 expression during LN remodeling after viral infection and LN reconstruction after avascular transplantation. Furthermore, IL-7–producing stromal cells contributed to de novo formation of LyveI-positive lymphatic structures connecting reconstructed LNs with the surrounding tissue. Importantly, diphtheria toxin–mediated depletion of IL-7–producing stromal cells completely abolished LN reconstruction. Taken together, this study identifies LN LECs as a major source of IL-7 and shows that IL-7–producing stromal cells are critical for reconstruction and remodeling of the distinct LN microenvironment.
- Published
- 2012