title: Lymph node T cell homeostasis relies on steady state homing of dendritic cells.
abstract: Little is known about mechanisms determining the homeostasis of lymphocytes within lymphoid organs. Applying different mouse models, including conditionally proficient Ccr7 gene-targeted mice, we now show that semimature steady state dendritic cells (sDCs) constitutively trafficking into lymph nodes (LNs) were essential contributors to T cell homeostasis in these organs. sDCs provided vascular endothelial growth factor known to support high endothelial venule formation, thus facilitating enhanced homing of T cells to LNs. The presence of sDCs led to increased CCL21 production in T-zone fibroblastic reticular cells. CCL21 is a ligand for CCR7 known to regulate homing as well as retention of T cells in LNs. In addition, we provide evidence that CCL21 binds to the surface of DCs via its heparin-binding domain, further explaining why T cells leave LNs more rapidly in the absence of sDCs. Together, these data reveal multiple roles for sDCs in regulating T cell homeostasis in LNs.
authors.affiliation: Institute of Immunology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Wendland
authors.forename: Stefanie
authors.initials: S
authors.lastname: Willenzon
authors.forename: Jessica
authors.initials: J
authors.lastname: Kocks
authors.forename: Ana Clara
authors.initials: AC
authors.lastname: Davalos-Misslitz
authors.forename: Swantje I
authors.initials: SI
authors.lastname: Hammerschmidt
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schumann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
authors.forename: Angelika
authors.initials: A
authors.lastname: Hoffmeyer
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D054421:Chemokine CCL21 / Q000378:metabolism; D046528:Chimerism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018390:Gene Targeting; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D054421:Chemokine CCL21; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D054400:Receptors, CCR7