Stimulating lymphotoxin β receptor on the dendritic cells is critical for their homeostasis and expansion

Yu Gang Wang, Kwang Dong Kim, Jing Wang, Ping Yu, Yang Xin Fu

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6997-7002
Number of pages6
JournalJournal of Immunology
Volume175
Issue number10
DOIs
StatePublished - Nov 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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