Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks

Deepali Malhotra, Anne L. Fletcher, Jillian Astarita, Veronika Lukacs-Kornek, Prakriti Tayalia, Santiago F. Gonzalez, Kutlu G. Elpek, Sook Kyung Chang, Konstantin Knoblich, Martin E. Hemler, Michael B. Brenner, Michael C. Carroll, David J. Mooney, Shannon J. Turley, Yan Zhou, Susan A. Shinton, Richard R. Hardy, Natalie A. Bezman, Joseph C. Sun, Charlie C. KimLewis L. Lanier, Jennifer Miller, Brian Brown, Miriam Merad, Angelique Bellemare-Pelletier, Kavitha Narayan, Katelyn Sylvia, Joonsoo Kang, Roi Gazit, Brian Garrison, Derrick J. Rossi, Vladimir Jojic, Daphne Koller, Radu Jianu, David Laidlaw, James Costello, Jim Collins, Nadia Cohen, Patrick Brennan, Tal Shay, Aviv Regev, Francis Kim, Tata Nageswara Rao, Amy Wagers, Emmanuel L. Gautier, Claudia Jakubzick, Gwendalyn J. Randolph, Paul Monach, Adam J. Best, Jamie Knell, Ananda Goldrath, Tracy Heng, Taras Kreslavsky, Michio Painter, Diane Mathis, Christophe Benoist

Research output: Contribution to journalArticlepeer-review

264 Scopus citations

Abstract

Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance, yet key aspects of their biology remain poorly elucidated. Here, comparative transcriptomic analyses of mouse LNSC subsets demonstrated the expression of important immune mediators, growth factors and previously unknown structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of crosstalk. Fibroblastic reticular cells (FRCs) showed enrichment for higher expression of genes relevant to cytokine signaling, relative to their expression in skin and thymic fibroblasts. LNSCs from inflamed lymph nodes upregulated expression of genes encoding chemokines and molecules involved in the acute-phase response and the antigen-processing and antigen-presentation machinery. Poorly studied podoplanin (gp38)-negative CD31- LNSCs showed similarities to FRCs but lacked expression of interleukin 7 (IL-7) and were identified as myofibroblastic pericytes that expressed integrin α7. Together our data comprehensively describe the transcriptional characteristics of LNSC subsets.

Original languageEnglish (US)
Pages (from-to)499-510
Number of pages12
JournalNature immunology
Volume13
Issue number5
DOIs
StatePublished - May 2012

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