title: IL-7-producing stromal cells are critical for lymph node remodeling.
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.
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St Gallen, St Gallen, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Onder
authors.forename: Priyanka
authors.initials: P
authors.lastname: Narang
authors.forename: Elke
authors.initials: E
authors.lastname: Scandella
authors.forename: Qian
authors.initials: Q
authors.lastname: Chai
authors.forename: Maria
authors.initials: M
authors.lastname: Iolyeva
authors.forename: Kerim
authors.initials: K
authors.lastname: Hoorweg
authors.forename: Cornelia
authors.initials: C
authors.lastname: Halin
authors.forename: Ellen
authors.initials: E
authors.lastname: Richie
authors.forename: Paul
authors.initials: P
authors.lastname: Kaye
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
authors.forename: Tom
authors.initials: T
authors.lastname: Cupedo
authors.forename: Mark
authors.initials: M
authors.lastname: Coles
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000196:embryology / Q000378:metabolism* / Q000637:transplantation; D042601:Lymphatic Vessels / Q000166:cytology / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D015851:Interleukin-7; D008164:Luminescent Proteins