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

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

Author information

1
Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.
2
Department of Pathology, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
3
Department of Rheumatology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA.
4
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA.
5
Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA; Pediatric Rheumatology, Hospital for Special Surgery, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, 10021, USA. Electronic address: lut@hss.edu.

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.

PMID:
25902483
PMCID:
PMC4591553
DOI:
10.1016/j.immuni.2015.03.015
[Indexed for MEDLINE]
Free PMC Article

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