TY - JOUR
T1 - Lymph Node T Cell Homeostasis Relies on Steady State Homing of Dendritic Cells
AU - Wendland, Meike
AU - Willenzon, Stefanie
AU - Kocks, Jessica
AU - Davalos-Misslitz, Ana Clara
AU - Hammerschmidt, Swantje I.
AU - Schumann, Kathrin
AU - Kremmer, Elisabeth
AU - Sixt, Michael
AU - Hoffmeyer, Angelika
AU - Pabst, Oliver
AU - Förster, Reinhold
N1 - Funding Information:
We thank I. Prinz for scientific discussions and G. Bernhardt for critically reading the manuscript. We thank W. Müller, Manchester, and B. Reizis, New York City, for providing Cd4-cre and Cd11c-cre mice, respectively. This work was supported by a Deutsche Forschungsgemeinschafts grants SFB621-A1 and SFB587-B3 to R.F. and Nycomed GmbH. A.H. is employee of Nycomed GmbH (Konstanz, Germany).
PY - 2011/12/23
Y1 - 2011/12/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84255177550&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2011.10.017
DO - 10.1016/j.immuni.2011.10.017
M3 - Article
C2 - 22195748
AN - SCOPUS:84255177550
SN - 1074-7613
VL - 35
SP - 945
EP - 957
JO - Immunity
JF - Immunity
IS - 6
ER -
