Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling

被引：60

作者：

Brown, Flavian D. ^{[1
,2
,3
,4
,5
,6
,14
]}

Sen, Debattama R. ^{[1
,2
]}

LaFleur, Martin W. ^{[1
,2
,3
,4
,5
]}

Godec, Jernej ^{[1
,2
,3
,4
,5
]}

Lukacs-Kornek, Veronika ^{[6
,15
]}

Schildberg, Frank A. ^{[3
,4
,5
,6
,16
]}

Kim, Hye-Jung ^{[3
,6
]}

Yates, Kathleen B. ^{[7
]}

Ricoult, Stephane J. H. ^{[8
]}

Bi, Kevin ^{[7
]}

Trombley, Justin D. ^{[3
,4
,5
]}

Kapoor, Varun N. ^{[9
]}

Stanley, Illana A. ^{[10
,11
]}

Cremasco, Viviana ^{[6
,17
]}

Danial, Nika N. ^{[10
,11
]}

Manning, Brendan D. ^{[8
]}

Sharpe, Arlene H. ^{[3
,4
,5
,7
,12
]}

Haining, W. Nicholas ^{[2
,7
,13
,18
]}

Turley, Shannon J. ^{[6
,9
]}

机构：

[1] Harvard Med Sch, Div Med Sci, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA

[3] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[4] Harvard Med Sch, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[6] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA USA

[7] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA

[8] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA USA

[9] Dept Canc Immunol Genentech, South San Francisco, CA USA

[10] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA

[11] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA

[12] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[13] Childrens Hosp, Div Pediat Hematol & Oncol, 300 Longwood Ave, Boston, MA 02115 USA

[14] Neon Therapeut Inc, Cambridge, MA USA

[15] Rhein Friedrich Wilhelms Univ Bonn, Inst Expt Immunol, Bonn, Germany

[16] Univ Hosp Bonn, Clin Orthoped & Trauma Surg, Bonn, Germany

[17] Novartis Inst BioMed Res, Immunooncol, Cambridge, MA USA

[18] Merck Res Labs, Boston, MA USA

来源：

NATURE IMMUNOLOGY | 2019年 / 20卷 / 12期

基金：

美国国家卫生研究院;

关键词：

LYMPH-NODE; NITRIC-OXIDE; DENDRITIC CELLS; STROMAL CELLS; CHROMATIN; IMMUNE; DIFFERENTIATION; HOMEOSTASIS; MIGRATION; GENE;

D O I：

10.1038/s41590-019-0515-x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Lymph node fibroblastic reticular cells (FRCs) respond to signals from activated T cells by releasing nitric oxide, which inhibits T cell proliferation and restricts the size of the expanding T cell pool. Whether interactions with FRCs also support the function or differentiation of activated CD8(+) T cells is not known. Here we report that encounters with FRCs enhanced cytokine production and remodeled chromatin accessibility in newly activated CD8(+) T cells via interleukin-6. These epigenetic changes facilitated metabolic reprogramming and amplified the activity of pro-survival pathways through differential transcription factor activity. Accordingly, FRC conditioning significantly enhanced the persistence of virus-specific CD8(+) T cells in vivo and augmented their differentiation into tissue-resident memory T cells. Our study demonstrates that FRCs play a role beyond restricting T cell expansion-they can also shape the fate and function of CD8(+) T cells.

引用

页码：1668 / +

页数：15

共 64 条

[1] Dendritic cells control fibroblastic reticular network tension and lymph node expansion
Acton, Sophie E.
Farrugia, Aaron J.
Astarita, Jillian L.
Mourao-Sa, Diego
Jenkins, Robert P.
Nye, Emma
Hooper, Steven
van Blijswijk, Janneke
Rogers, Neil C.
Snelgrove, Kathryn J.
Rosewell, Ian
Moita, Luis F.
Stamp, Gordon
Turley, Shannon J.
Sahai, Erik
Reis e Sousa, Caetano
[J]. NATURE, 2014, 514 (7523) : 498 - +
[2] Stromal cell networks coordinate immune response generation and maintenance
Alexandre, Yannick O.
Mueller, Scott N.
[J]. IMMUNOLOGICAL REVIEWS, 2018, 283 (01) : 77 - 85
[3] CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3-kinase independent manner
Asperti-Boursin, Francois
Real, Eliana
Bismuth, Georges
Trautmann, Alain
Donnadieu, Emmanuel
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (05) : 1167 - 1179
[4] The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture
Astarita, Jillian L.
Cremasco, Viviana
Fu, Jianxin
Darnell, Max C.
Peck, James R.
Nieves-Bonilla, Janice M.
Song, Kai
Kondo, Yuji
Woodruff, Matthew C.
Gogineni, Alvin
Onder, Lucas
Ludewig, Burkhard
Weimer, Robby M.
Carroll, Michael C.
Mooney, David J.
Xia, Lijun
Turley, Shannon J.
[J]. NATURE IMMUNOLOGY, 2015, 16 (01) : 75 - +
[5] Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes
Bajenoff, Marc
Egen, Jackson G.
Koo, Lily Y.
Laugier, Jean Pierre
Brau, Frederic
Glaichenhaus, Nicolas
Germain, Ronald N.
[J]. IMMUNITY, 2006, 25 (06) : 989 - 1001
[6] Fibroblastic Reticular Cells: Organization and Regulation of the T Lymphocyte Life Cycle
Brown, Flavian D.
Turley, Shannon J.
[J]. JOURNAL OF IMMUNOLOGY, 2015, 194 (04) : 1389 - 1394
[7] Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase
Brown, GC
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2001, 1504 (01): : 46 - 57
[8] T cell metabolism drives immunity
Buck, Michael D.
O'Sullivan, David
Pearce, Erika L.
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2015, 212 (09) : 1345 - 1360
[9] Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]
[10] Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis
Chang, Chih-Hao
Curtis, Jonathan D.
Maggi, Leonard B., Jr.
Faubert, Brandon
Villarino, Alejandro V.
O'Sullivan, David
Huang, Stanley Ching-Cheng
van der Windt, Gerritje J. W.
Blagih, Julianna
Qiu, Jing
Weber, Jason D.
Pearce, Edward J.
Jones, Russell G.
Pearce, Erika L.
[J]. CELL, 2013, 153 (06) : 1239 - 1251

← 1 2 3 4 5 6 7 →