Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity

被引：395

作者：

Kidani, Yoko ^{[1
,2
]}

Elsaesser, Heidi ^{[3
,4
]}

Hock, M. Benjamin ^{[1
,2
]}

Vergnes, Laurent ^{[5
]}

Williams, Kevin J. ^{[1
,2
]}

Argus, Joseph P. ^{[1
,6
]}

Marbois, Beth N. ^{[1
,7
]}

Komisopoulou, Evangelia ^{[6
,8
]}

Wilson, Elizabeth B. ^{[3
,4
]}

Osborne, Timothy F. ^{[9
]}

Graeber, Thomas G. ^{[1
,6
,8
]}

Reue, Karen ^{[5
,10
,11
]}

Brooks, David G. ^{[3
,4
]}

Bensinger, Steven J. ^{[1
,2
,6
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA

[9] Sanford Burnham Med Res Inst, Diabet & Obes Ctr, Metab Signaling & Dis Program, Orlando, FL USA

[10] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[11] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 05期

基金：

美国国家卫生研究院;

关键词：

FATTY-ACID SYNTHESIS; ANTIGEN RECEPTOR; LIPID RAFTS; CHOLESTEROL; MEMORY; MICE; HOMEOSTASIS; ACTIVATION; PATHWAY; MYC;

D O I：

10.1038/ni.2570

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Newly activated CD8(+) T cells reprogram their metabolism to meet the extraordinary biosynthetic demands of clonal expansion; however, the signals that mediate metabolic reprogramming remain poorly defined. Here we demonstrate an essential role for sterol regulatory element-binding proteins (SREBPs) in the acquisition of effector-cell metabolism. Without SREBP signaling, CD8(+) T cells were unable to blast, which resulted in attenuated clonal expansion during viral infection. Mechanistic studies indicated that SREBPs were essential for meeting the heightened lipid requirements of membrane synthesis during blastogenesis. SREBPs were dispensable for homeostatic proliferation, which indicated a context-specific requirement for SREBPs in effector responses. Our studies provide insights into the molecular signals that underlie the metabolic reprogramming of CD8(+) T cells during the transition from quiescence to activation.

引用

页码：489 / +

页数：13

共 37 条

[1] SELECTION OF GENETIC-VARIANTS OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN SPLEENS OF PERSISTENTLY INFECTED MICE - ROLE IN SUPPRESSION OF CYTO-TOXIC LYMPHOCYTE-T RESPONSE AND VIRAL PERSISTENCE
AHMED, R
SALMI, A
BUTLER, LD
CHILLER, JM
OLDSTONE, MBA
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (02) : 521 - 540
[2] mTOR regulates memory CD8 T-cell differentiation
Araki, Koichi
Turner, Alexandra P.
Shaffer, Virginia Oliva
Gangappa, Shivaprakash
Keller, Susanne A.
Bachmann, Martin F.
Larsen, Christian P.
Ahmed, Rafi
[J]. NATURE, 2009, 460 (7251) : 108 - U124
[3] LXR signaling couples sterol metabolism to proliferation in the acquired immune response
Bensinger, Steven J.
Bradley, Michelle N.
Joseph, Sean B.
Zelcer, Noam
Janssen, Edith M.
Hausner, Mary Ann
Shih, Roger
Parks, John S.
Edwards, Peter A.
Jamieson, Beth D.
Tontonoz, Peter
[J]. CELL, 2008, 134 (01) : 97 - 111
[4] Boren J, 2001, J BIOL CHEM, V276, P37747
[5] Intrinsic functional dysregulation of CD4 T cells occurs rapidly following persistent viral infection
Brooks, DG
Teyton, L
Oldstone, MBA
McGavern, DB
[J]. JOURNAL OF VIROLOGY, 2005, 79 (16) : 10514 - 10527
[6] Glutamine Uptake and Metabolism Are Coordinately Regulated by ERK/MAPK during T Lymphocyte Activation
Carr, Erikka L.
Kelman, Alina
Wu, Glendon S.
Gopaul, Ravindra
Senkevitch, Emilee
Aghvanyan, Anahit
Turay, Achmed M.
Frauwirth, Kenneth A.
[J]. JOURNAL OF IMMUNOLOGY, 2010, 185 (02) : 1037 - 1044
[7] Transcriptional regulation of phagocytosis-induced membrane biogenesis by sterol regulatory element binding proteins
Castoreno, AB
Wang, Y
Stockinger, W
Jarzylo, LA
Du, H
Pagnon, JC
Shieh, EC
Nohturfft, A
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (37) : 13129 - 13134
[8] CHAKRABARTI R, 1991, J BIOL CHEM, V266, P12216
[9] RELATIONSHIP BETWEEN STEROL SYNTHESIS AND DNA-SYNTHESIS IN PHYTOHEMAGGLUTININ-STIMULATED MOUSE LYMPHOCYTES
CHEN, HW
HEINIGER, HJ
KANDUTSCH, AA
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1975, 72 (05) : 1950 - 1954
[10] Hypoxia and metabolism - Opinion - The interplay between MYC and HIF in cancer
Dang, Chi V.
Kim, Jung-whan
Gao, Ping
Yustein, Jason
[J]. NATURE REVIEWS CANCER, 2008, 8 (01) : 51 - 56

← 1 2 3 4 →