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.
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Acknowledgements
We thank L. Fisher (US National Institutes of Health) for polyclonal anti-decorin, anti-fibromodulin and anti-biglycan; M. Koch (University of Cologne) for polyclonal anti–collagen XIV; M. Curry for technical assistance in sorting stromal-cell populations; J.B. Lewis for discussions during analysis of microarray data; eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project; and K.W. Wucherpfennig for critical reading of the manuscript. Supported by the US National Institutes of Health (R01 DK074500 and P01 AI045757 to S.J.T.; R24 AI072073 to the ImmGen Consortium; R01 AI063428-06 to M.B.B.; R01 DE019917 to D.J.M.; and GM38903 to M.E.H. and K.K.), the Dana-Farber Cancer Institute (K.K. and V.L.-K.) and the Seventh Framework Programme of the European Union (Marie Curie International Outgoing Fellowship 220044 to S.F.G.).
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D.M. and A.L.F. designed the study, did and analyzed most experiments, and wrote the manuscript; S.J.T. designed and directed the study, analyzed and interpreted results, and wrote the manuscript; D.M. did primary analysis of the microarray data; V.L.-K., P.T., S.F.G., J.A., K.G.E. and K.K. did and analyzed individual experiments; and S.K.C., M.B.B., D.J.M., M.C.C. and M.E.H. contributed reagents and assisted with the analysis of individual experiments.
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Malhotra, D., Fletcher, A., Astarita, J. et al. Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks. Nat Immunol 13, 499–510 (2012). https://doi.org/10.1038/ni.2262
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DOI: https://doi.org/10.1038/ni.2262
