Publication

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

Journal Paper/Review - Sep 6, 2012

Units
PubMed
Doi

Citation
Onder L, Coles M, Cupedo T, Westermann J, Kaye P, Richie E, Halin C, Hoorweg K, Iolyeva M, Chai Q, Scandella E, Narang P, Ludewig B. IL-7-producing stromal cells are critical for lymph node remodeling. Blood 2012; 120:4675-83.
Type
Journal Paper/Review (English)
Journal
Blood 2012; 120
Publication Date
Sep 6, 2012
Issn Electronic
1528-0020
Pages
4675-83
Brief description/objective

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.