TY - JOUR
T1 - Stimulating lymphotoxin β receptor on the dendritic cells is critical for their homeostasis and expansion
AU - Wang, Yu Gang
AU - Kim, Kwang Dong
AU - Wang, Jing
AU - Yu, Ping
AU - Fu, Yang Xin
PY - 2005/11/15
Y1 - 2005/11/15
N2 - The increased number of dendritic cells (DCs) inside lymphoid tissue may contribute to the enhanced priming of lymphocytes. The homeostasis of splenic DCs has mostly been attributed to their migration to the spleen via the chemokine microenvironment induced by lymphotoxin β receptor (LTβR) signaling on splenic stromal cells. In this study we show that the lack of direct LTβR signaling on DCs is associated with the reduction of the number of DCs in the spleen independently of chemokine gradients. LTβR -/- mice have reduced DCs and reduced BrdU incorporation on DCs, and fewer DCs from LTβR-/- mice are detected in the spleen. Furthermore, increased expression of LIGHT (homologous to lymphotoxin, exhibits inducible expression, competes with herpesvirus glycoprotein D for herpes virus entry mediator on T cells) on T cells, a member of the TNF family (TNFSF14) and a ligand for LTβR, could dramatically increase the number of T cells and DCs, which leads to severe autoimmune diseases in a LTβR-dependent fashion. In vitro, LIGHT could directly promote accumulation of bone marrow-derived DCs. Furthermore, intratumor expression of LIGHT can dramatically expand DCs in situ, and inoculation of DCs into tumor tissues enhanced tumor immunity. Therefore, LTβR signaling on DCs is required for their homeostasis during physiology and pathological conditions, and increased LIGHT-LTβR interaction could stimulate DC expansion for T cell-mediated immunity.
AB - The increased number of dendritic cells (DCs) inside lymphoid tissue may contribute to the enhanced priming of lymphocytes. The homeostasis of splenic DCs has mostly been attributed to their migration to the spleen via the chemokine microenvironment induced by lymphotoxin β receptor (LTβR) signaling on splenic stromal cells. In this study we show that the lack of direct LTβR signaling on DCs is associated with the reduction of the number of DCs in the spleen independently of chemokine gradients. LTβR -/- mice have reduced DCs and reduced BrdU incorporation on DCs, and fewer DCs from LTβR-/- mice are detected in the spleen. Furthermore, increased expression of LIGHT (homologous to lymphotoxin, exhibits inducible expression, competes with herpesvirus glycoprotein D for herpes virus entry mediator on T cells) on T cells, a member of the TNF family (TNFSF14) and a ligand for LTβR, could dramatically increase the number of T cells and DCs, which leads to severe autoimmune diseases in a LTβR-dependent fashion. In vitro, LIGHT could directly promote accumulation of bone marrow-derived DCs. Furthermore, intratumor expression of LIGHT can dramatically expand DCs in situ, and inoculation of DCs into tumor tissues enhanced tumor immunity. Therefore, LTβR signaling on DCs is required for their homeostasis during physiology and pathological conditions, and increased LIGHT-LTβR interaction could stimulate DC expansion for T cell-mediated immunity.
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U2 - 10.4049/jimmunol.175.10.6997
DO - 10.4049/jimmunol.175.10.6997
M3 - Article
C2 - 16272360
AN - SCOPUS:27744442642
SN - 0022-1767
VL - 175
SP - 6997
EP - 7002
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -