IL-7-producing stromal cells are critical for lymph node remodeling
Research output: Contribution to journal › Article › peer-review
Non-hematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures such as lymph node 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. Interleukin-7 (IL-7) is an important stromal cell-derived cytokine that has been considered to be derived mainly from T cell zone fibroblastic reticular cells (FRCs). We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7 both in human and murine lymph nodes. Using BAC transgenic IL-7-Cre mice, we found that FRCs and LECs strongly upregulated IL-7 expression during LN remodeling following 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.