Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks
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 s...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/85101 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826207900450684928 |
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| author | Regev, Aviv Immunological Genome Project Consortium |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv Immunological Genome Project Consortium |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:56:44Z |
| format | Article |
| id | mit-1721.1/85101 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:56:44Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
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| spelling | mit-1721.1/851012022-09-28T17:17:15Z Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks Regev, Aviv Immunological Genome Project Consortium Massachusetts Institute of Technology. Department of Biology Regev, Aviv 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. National Institutes of Health (U.S.) (grant R01 DK074500) National Institutes of Health (U.S.) (grant P01 AI045757) National Institutes of Health (U.S.) (grant R24 AI072073) National Institutes of Health (U.S.) (grant R01 AI063428-06) National Institutes of Health (U.S.) (grant R01 DE019917) National Institutes of Health (U.S.) (grant GM38903) Dana-Farber Cancer Institute Seventh Framework Programme of the European Union (Marie Curie International Outgoing Fellowship 220044) 2014-02-26T19:23:31Z 2014-02-26T19:23:31Z 2012-04 2011-08 Article http://purl.org/eprint/type/JournalArticle 1529-2908 1529-2916 http://hdl.handle.net/1721.1/85101 Malhotra, Deepali, Anne L Fletcher, Jillian Astarita, Veronika Lukacs-Kornek, Prakriti Tayalia, Santiago F Gonzalez, Kutlu G Elpek, et al. “Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks.” Nature Immunology 13, no. 5 (April 1, 2012): 499-510. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1038/ni.2262 Nature Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Regev, Aviv Immunological Genome Project Consortium Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks |
| title | Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks |
| title_full | Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks |
| title_fullStr | Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks |
| title_full_unstemmed | Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks |
| title_short | Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks |
| title_sort | transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks |
| url | http://hdl.handle.net/1721.1/85101 https://orcid.org/0000-0001-8567-2049 |
| work_keys_str_mv | AT regevaviv transcriptionalprofilingofstromafrominflamedandrestinglymphnodesdefinesimmunologicalhallmarks AT immunologicalgenomeprojectconsortium transcriptionalprofilingofstromafrominflamedandrestinglymphnodesdefinesimmunologicalhallmarks |