A Dendritic-Cell-Stromal Axis Maintains Immune Responses in Lymph Nodes

Varsha Kumar, Dragos C. Dasoveanu, Susan Chyou, Te Chen Tzeng, Cristina Rozo, Yong Liang, William Stohl, Yang Xin Fu, Nancy H. Ruddle, Theresa T. Lu

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)719-730
Number of pages12
JournalImmunity
Volume42
Issue number4
DOIs
StatePublished - Apr 21 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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