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 C Miller, Brian D Brown, Miriam Merad, Angelique Bellemare-Pelletier, Kavitha Narayan, Katelyn Sylvia, Joonsoo Kang, Roi Gazit, Brian S Garrison, Derrick J Rossi, Vladimir Jojic, Daphne Koller, Radu Jianu, David H Laidlaw, James C Costello, Jim J Collins, Nadia R Cohen, Patrick J Brennan, Tal Shay, Aviv Regev, Francis S Kim, Tata N Rao, Amy Wagers, Emmanuel L Gautier, Claudia V Jakubzick, Gwendalyn J Randolph, Paul Monach, J Adam Best, Jamie Knell, Ananda W Goldrath, Tracy S P Heng, Taras Kreslavsky, Michio W Painter, Diane Mathis, Christophe Benoist

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257 Citations (Scopus)

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 alpha(7). Together our data comprehensively describe the transcriptional characteristics of LNSC subsets.
Original languageEnglish
Pages (from-to)499 - 510
Number of pages12
JournalNature Immunology
Volume13
Issue number5
DOIs
Publication statusPublished - 2012
Externally publishedYes

Cite this

Malhotra, D., Fletcher, A. L., Astarita, J., Lukacs-Kornek, V., Tayalia, P., Gonzalez, S. F., Elpek, K. G., Chang, S. K., Knoblich, K., Hemler, M. E., Brenner, M. B., Carroll, M. C., Mooney, D. J., Turley, S. J., Zhou, Y., Shinton, S. A., Hardy, R. R., Bezman, N. A., Sun, J. C., ... Benoist, C. (2012). Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks. Nature Immunology, 13(5), 499 - 510. https://doi.org/10.1038/ni.2262