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. Kim; Lewis 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

doi:10.1038/ni.2262

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

Medical School - Twin Cities Campus

Research output: Contribution to journal › Article › peer-review

365 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 language	English (US)
Pages (from-to)	499-510
Number of pages	12
Journal	Nature immunology
Volume	13
Issue number	5
DOIs	https://doi.org/10.1038/ni.2262
State	Published - May 2012

Bibliographical note

Funding Information:
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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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

Malhotra, D, Fletcher, AL, Astarita, J, Lukacs-Kornek, V, Tayalia, P, Gonzalez, SF, Elpek, KG, Chang, SK, Knoblich, K, Hemler, ME, Brenner, MB, Carroll, MC, Mooney, DJ, Turley, SJ, Zhou, Y, Shinton, SA, Hardy, RR, Bezman, NA, Sun, JC, Kim, CC, Lanier, LL, Miller, J, Brown, B, Merad, M, Bellemare-Pelletier, A, Narayan, K, Sylvia, K, Kang, J, Gazit, R, Garrison, B, Rossi, DJ, Jojic, V, Koller, D, Jianu, R, Laidlaw, D, Costello, J, Collins, J, Cohen, N, Brennan, P, Shay, T, Regev, A, Kim, F, Rao, TN, Wagers, A, Gautier, EL, Jakubzick, C, Randolph, GJ, Monach, P, Best, AJ, Knell, J, Goldrath, A, Heng, T, Kreslavsky, T, Painter, M, Mathis, D & Benoist, C 2012, 'Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks', Nature immunology, vol. 13, no. 5, pp. 499-510. https://doi.org/10.1038/ni.2262

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title = "Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks",

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.",

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

note = "Funding Information: 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.).",

year = "2012",

month = may,

doi = "10.1038/ni.2262",

language = "English (US)",

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pages = "499--510",

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T1 - Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks

AU - Malhotra, Deepali

AU - Fletcher, Anne L.

AU - Astarita, Jillian

AU - Lukacs-Kornek, Veronika

AU - Tayalia, Prakriti

AU - Gonzalez, Santiago F.

AU - Elpek, Kutlu G.

AU - Chang, Sook Kyung

AU - Knoblich, Konstantin

AU - Hemler, Martin E.

AU - Brenner, Michael B.

AU - Carroll, Michael C.

AU - Mooney, David J.

AU - Turley, Shannon J.

AU - Zhou, Yan

AU - Shinton, Susan A.

AU - Hardy, Richard R.

AU - Bezman, Natalie A.

AU - Sun, Joseph C.

AU - Kim, Charlie C.

AU - Lanier, Lewis L.

AU - Miller, Jennifer

AU - Brown, Brian

AU - Merad, Miriam

AU - Bellemare-Pelletier, Angelique

AU - Narayan, Kavitha

AU - Sylvia, Katelyn

AU - Kang, Joonsoo

AU - Gazit, Roi

AU - Garrison, Brian

AU - Rossi, Derrick J.

AU - Jojic, Vladimir

AU - Koller, Daphne

AU - Jianu, Radu

AU - Laidlaw, David

AU - Costello, James

AU - Collins, Jim

AU - Cohen, Nadia

AU - Brennan, Patrick

AU - Shay, Tal

AU - Regev, Aviv

AU - Kim, Francis

AU - Rao, Tata Nageswara

AU - Wagers, Amy

AU - Gautier, Emmanuel L.

AU - Jakubzick, Claudia

AU - Randolph, Gwendalyn J.

AU - Monach, Paul

AU - Best, Adam J.

AU - Knell, Jamie

AU - Goldrath, Ananda

AU - Heng, Tracy

AU - Kreslavsky, Taras

AU - Painter, Michio

AU - Mathis, Diane

AU - Benoist, Christophe

N1 - Funding Information: 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.).

PY - 2012/5

Y1 - 2012/5

N2 - 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.

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

Abstract

Bibliographical note

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