IL-7–producing stromal cells are critical for lymph node remodeling

Author:

Onder Lucas1,Narang Priyanka2,Scandella Elke1,Chai Qian1,Iolyeva Maria3,Hoorweg Kerim4,Halin Cornelia3,Richie Ellen5,Kaye Paul2,Westermann Jürgen6,Cupedo Tom5,Coles Mark2,Ludewig Burkhard1

Affiliation:

1. Institute of Immunobiology, Kantonal Hospital St Gallen, St Gallen, Switzerland;

2. Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, York, United Kingdom;

3. Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland;

4. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands;

5. MD Anderson Cancer Center, Smithville, TX; and

6. Institute of Anatomy, University of Lübeck, Lübeck, Germany

Abstract

AbstractNonhematopoietic 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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