TY - JOUR
T1 - A Dendritic-Cell-Stromal Axis Maintains Immune Responses in Lymph Nodes
AU - Kumar, Varsha
AU - Dasoveanu, Dragos C.
AU - Chyou, Susan
AU - Tzeng, Te Chen
AU - Rozo, Cristina
AU - Liang, Yong
AU - Stohl, William
AU - Fu, Yang Xin
AU - Ruddle, Nancy H.
AU - Lu, Theresa T.
N1 - Funding Information:
We acknowledge everyone in the Lu lab for helping hands, Alessandra Pernis and Jane Salmon and labs for helpful discussions, Michel Nussenzweig for zDC-DTR mice, and Jeff Browning and Adrian Erlebacher for helpful comments on the manuscript. This work was supported by R01 AI079178 (T.L.), the Alliance for Lupus Research (T.L.), and the St. Giles Foundation (T.L.).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/21
Y1 - 2015/4/21
N2 - Within secondary lymphoid tissues, stromal reticular cells support lymphocyte function, and targeting reticular cells is a potential strategy for controlling pathogenic lymphocytes in disease. However, the mechanisms that regulate reticular cell function are not well understood. Here we found that during an immune response in lymph nodes, dendritic cells (DCs) maintain reticular cell survival in multiple compartments. DC-derived lymphotoxin beta receptor (LTβR) ligands were critical mediators, and LTβR signaling on reticular cells mediated cell survival by modulating podoplanin (PDPN). PDPN modulated integrin-mediated cell adhesion, which maintained cell survival. This DC-stromal axis maintained lymphocyte survival and the ongoing immune response. Our findings provide insight into the functions of DCs, LTβR, and PDPN and delineate a DC-stromal axis that can potentially be targeted in autoimmune or lymphoproliferative diseases.
AB - Within secondary lymphoid tissues, stromal reticular cells support lymphocyte function, and targeting reticular cells is a potential strategy for controlling pathogenic lymphocytes in disease. However, the mechanisms that regulate reticular cell function are not well understood. Here we found that during an immune response in lymph nodes, dendritic cells (DCs) maintain reticular cell survival in multiple compartments. DC-derived lymphotoxin beta receptor (LTβR) ligands were critical mediators, and LTβR signaling on reticular cells mediated cell survival by modulating podoplanin (PDPN). PDPN modulated integrin-mediated cell adhesion, which maintained cell survival. This DC-stromal axis maintained lymphocyte survival and the ongoing immune response. Our findings provide insight into the functions of DCs, LTβR, and PDPN and delineate a DC-stromal axis that can potentially be targeted in autoimmune or lymphoproliferative diseases.
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U2 - 10.1016/j.immuni.2015.03.015
DO - 10.1016/j.immuni.2015.03.015
M3 - Article
C2 - 25902483
AN - SCOPUS:84928201383
SN - 1074-7613
VL - 42
SP - 719
EP - 730
JO - Immunity
JF - Immunity
IS - 4
ER -