title: A dendritic-cell-stromal axis maintains immune responses in lymph nodes.
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.
authors.affiliation: Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.
authors.forename: Varsha
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.
authors.forename: Dragos C
authors.initials: DC
authors.lastname: Dasoveanu
authors.affiliation: Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Chyou
authors.affiliation: Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.
authors.forename: Te-Chen
authors.initials: TC
authors.lastname: Tzeng
authors.affiliation: Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rozo
authors.affiliation: Department of Pathology, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Rheumatology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA.
authors.forename: William
authors.initials: W
authors.lastname: Stohl
authors.affiliation: Department of Pathology, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA.
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Ruddle
authors.affiliation: 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.
authors.forename: Theresa T
authors.initials: TT
authors.lastname: Lu
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002470:Cell Survival / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005786:Gene Expression Regulation; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008212:Lymphocyte Depletion; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology* / Q000276:immunology; D000098853:Podoplanin
chemical_list: D053259:Lymphotoxin beta Receptor; D008562:Membrane Glycoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C505699:Ltbr protein, mouse