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 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

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 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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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 language	English
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
Publication status	Published - 2012
Externally published	Yes

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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

@article{51093b1012904b579c91983784b50546,

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 alpha(7). 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 Miller, {Jennifer C} and Brown, {Brian D} and Miriam Merad and Angelique Bellemare-Pelletier and Kavitha Narayan and Katelyn Sylvia and Joonsoo Kang and Roi Gazit and Garrison, {Brian S} and Rossi, {Derrick J} and Vladimir Jojic and Daphne Koller and Radu Jianu and Laidlaw, {David H} and Costello, {James C} and Collins, {Jim J} and Cohen, {Nadia R} and Brennan, {Patrick J} and Tal Shay and Aviv Regev and Kim, {Francis S} and Rao, {Tata N} and Amy Wagers and Gautier, {Emmanuel L} and Jakubzick, {Claudia V} and Randolph, {Gwendalyn J} and Paul Monach and Best, {J Adam} and Jamie Knell and Goldrath, {Ananda W} and Heng, {Tracy S P} and Taras Kreslavsky and Painter, {Michio W} and Diane Mathis and Christophe Benoist",

year = "2012",

doi = "10.1038/ni.2262",

language = "English",

volume = "13",

pages = "499 -- 510",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "5",

}

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, JC, Brown, BD, Merad, M, Bellemare-Pelletier, A, Narayan, K, Sylvia, K, Kang, J, Gazit, R, Garrison, BS, Rossi, DJ, Jojic, V, Koller, D, Jianu, R, Laidlaw, DH, Costello, JC, Collins, JJ, Cohen, NR, Brennan, PJ, Shay, T, Regev, A, Kim, FS, Rao, TN, Wagers, A, Gautier, EL, Jakubzick, CV, Randolph, GJ, Monach, P, Best, JA, Knell, J, Goldrath, AW, Heng, TSP, Kreslavsky, T, Painter, MW, 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

TY - JOUR

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 C

AU - Brown, Brian D

AU - Merad, Miriam

AU - Bellemare-Pelletier, Angelique

AU - Narayan, Kavitha

AU - Sylvia, Katelyn

AU - Kang, Joonsoo

AU - Gazit, Roi

AU - Garrison, Brian S

AU - Rossi, Derrick J

AU - Jojic, Vladimir

AU - Koller, Daphne

AU - Jianu, Radu

AU - Laidlaw, David H

AU - Costello, James C

AU - Collins, Jim J

AU - Cohen, Nadia R

AU - Brennan, Patrick J

AU - Shay, Tal

AU - Regev, Aviv

AU - Kim, Francis S

AU - Rao, Tata N

AU - Wagers, Amy

AU - Gautier, Emmanuel L

AU - Jakubzick, Claudia V

AU - Randolph, Gwendalyn J

AU - Monach, Paul

AU - Best, J Adam

AU - Knell, Jamie

AU - Goldrath, Ananda W

AU - Heng, Tracy S P

AU - Kreslavsky, Taras

AU - Painter, Michio W

AU - Mathis, Diane

AU - Benoist, Christophe

PY - 2012

Y1 - 2012

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 alpha(7). 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 alpha(7). Together our data comprehensively describe the transcriptional characteristics of LNSC subsets.

UR - http://www.ncbi.nlm.nih.gov/pubmed/22466668

U2 - 10.1038/ni.2262

DO - 10.1038/ni.2262

M3 - Article

SN - 1529-2908

VL - 13

SP - 499

EP - 510

JO - Nature Immunology

JF - Nature Immunology

IS - 5

ER -

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

Abstract

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