A dendritic-cell-stromal axis maintains immune responses in lymph nodes

Immunity. 2015 Apr 21;42(4):719-30. doi: 10.1016/j.immuni.2015.03.015.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Survival / immunology
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Gene Expression Regulation
  • Immunophenotyping
  • Lymph Nodes / cytology*
  • Lymph Nodes / immunology
  • Lymphocyte Depletion
  • Lymphotoxin beta Receptor / genetics
  • Lymphotoxin beta Receptor / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Signal Transduction
  • Stromal Cells / cytology*
  • Stromal Cells / immunology

Substances

  • Gp38 protein, mouse
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Membrane Glycoproteins