Tryptophan catabolism generates autoimmune-preventive regulatory T cells

被引：96

作者：

Fallarino, Francesca

Grohmann, Ursula

You, Sylvaine

McGrath, Barbara C.

Cavener, Douglas R.

Vacca, Carmine

Orabona, Ciriana

Bianchi, Roberta

Belladonna, Maria L.

Volpi, Claudia

Fioretti, Maria C.

Puccetti, Paolo

机构：

[1] Univ Perugia, Pharmacol Sect, Dept Expt Med, I-06126 Perugia, Italy

[2] Hop Necker Enfants Malad, INSERM, U580, IRNEM, F-75015 Paris, France

[3] Penn State Univ, Dept Biol, University Pk, PA 16802 USA

来源：

TRANSPLANT IMMUNOLOGY | 2006年 / 17卷 / 01期

关键词：

dendritic cells; regulatory T cells; tryptophan;

D O I：

10.1016/j.trim.2006.09.017

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tryptophan catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan catabolism affects T cell responses remain unclear. We provide evidence that its effects include the emergence of a regulatory phenotype in naive CD4(+)CD25(-) cells via the general control non-depressing 2 (GCN2) protein kinase mediated induction of the forkhead transcription factor Foxp3. These cells are capable of effective control of diabetogenic T cells in vivo. (c) 2006 Elsevier B.V. All rights reserved.

引用

收藏

页码：58 / 60

页数：3

相关论文

共 12 条

[1] Diversity of regulatory CD4+ T cells controlling distinct organ-specific autoimmune diseases [J].

Alyanakian, MA ;

You, S ;

Damotte, D ;

Gouarin, C ;

Esling, A ;

Garcia, C ;

Havouis, S ;

Chatenoud, L ;

Bach, JF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (26) :15806-15811

[2] Origin of regulatory T cells with known specificity for antigen [J].

Apostolou, I ;

Sarukhan, A ;

Klein, L ;

von Boehmer, H .

NATURE IMMUNOLOGY, 2002, 3 (08) :756-763

[3] Modulation of tryptophan catabolism by regulatory T cells [J].

Fallarino, F ;

Grohmann, U ;

Hwang, KW ;

Orabona, C ;

Vacca, C ;

Bianchi, R ;

Belladonna, ML ;

Fioretti, MC ;

Alegre, ML ;

Puccetti, P .

NATURE IMMUNOLOGY, 2003, 4 (12) :1206-1212

[4] T cell apoptosis by tryptophan catabolism [J].

Fallarino, I ;

Grohmann, U ;

Vacca, C ;

Bianchi, R ;

Orabona, C ;

Spreca, A ;

Fioretti, MC ;

Puccetti, P .

CELL DEATH AND DIFFERENTIATION, 2002, 9 (10) :1069-1077

[5] CD4+ Tregs and immune control [J].

Fehérvari, Z ;

Sakaguchi, S .

JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (09) :1209-1217

[6] CTLA-4-Ig regulates tryptophan catabolism in vivo [J].

Grohmann, U ;

Orabona, C ;

Fallarino, F ;

Vacca, C ;

Calcinaro, F ;

Falorni, A ;

Candeloro, P ;

Belladonna, ML ;

Bianchi, R ;

Fioretti, MC ;

Puccetti, P .

NATURE IMMUNOLOGY, 2002, 3 (11) :1097-1101

[7] Tolerance, DCs and tryptophan: much ado about IDO [J].

Grohmann, U ;

Fallarino, F ;

Puccetti, P .

TRENDS IN IMMUNOLOGY, 2003, 24 (05) :242-248

[8] IDO expression by dendritic cells: Tolerance and tryptophan catabolism [J].

Mellor, AL ;

Munn, DH .

NATURE REVIEWS IMMUNOLOGY, 2004, 4 (10) :762-774

[9] GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase [J].

Munn, DH ;

Sharma, MD ;

Baban, B ;

Harding, HP ;

Zhang, YH ;

Ron, D ;

Mellor, AL .

IMMUNITY, 2005, 22 (05) :633-642

[10] Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite [J].

Platten, M ;

Ho, PP ;

Youssef, S ;

Fontoura, P ;

Garren, H ;

Hur, EM ;

Gupta, R ;

Lee, LY ;

Kidd, BA ;

Robinson, WH ;

Sobel, RA ;

Selley, ML ;

Steinman, L .

SCIENCE, 2005, 310 (5749) :850-855