IL-1β and IL-2 convert human Treg into TH17 cells

被引：145

作者：

Deknuydt, Florence ^{[1
]}

Bioley, Gilles ^{[1
]}

Valmori, Danila ^{[1
,2
]}

Ayyoub, Maha ^{[1
]}

机构：

[1] CLCC Rene Gauducheau, Inst Natl Sante & Rech Med, U892, F-44800 St Herblain, France

[2] Univ Nantes, Fac Med, F-44093 Nantes, France

来源：

CLINICAL IMMUNOLOGY | 2009年 / 131卷 / 02期

关键词：

Treg; T(H)17; IL-1; beta; IL-2; GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TOLL-LIKE; TGF-BETA; T-CELLS; CUTTING EDGE; DIFFERENTIATION; EXPRESSION; FOXP3; INTERLEUKIN-1-BETA;

D O I：

10.1016/j.clim.2008.12.008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Natural CD4(+)CD25(+) regulatory T cells (Treg) and interleukin 17 (IL-17)-producing T helper cells (T(H)17) carry out opposite functions, the former maintaining self-tolerance and the latter being involved in inflammation and autoimmunity. We report here that stimulation of human Natural Treg under T(H)17 polarizing conditions in the presence of IL-2 converts them into T(H)17 cells. Conversion of Tregs into T(H)17 cells occurs both from natural naive Tregs (NnTregs) and, to a higher extent, from memory Tregs (MTregs). Among antigen presenting cells, fresh monocytes activated by microbial stimuli were the most efficient inducers of T(H)17 cells from Tregs. Conversion of Treg into T(H)17 cells was induced by IL-1 beta and involved down-regulation of the Treg lineage transcription factor FOXP3 and suppressive functions. Our results indicate that, under inflammatory conditions, in the presence of IL-2, Treg can be converted into pro-inflammatory T(H)17 cells and establish a functional link between inflammation and autoimmunity. (C) 2009 Elsevier Inc. All. rights reserved.

引用

页码：298 / 307

页数：10

共 47 条

[1] Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells [J].

Acosta-Rodriguez, Eva V. ;

Napolitani, Giorgio ;

Lanzavecchia, Antonio ;

Sallusto, Federica .

NATURE IMMUNOLOGY, 2007, 8 (09) :942-949

[2] Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells [J].

Acosta-Rodriguez, Eva V. ;

Rivino, Laura ;

Geginat, Jens ;

Jarrossay, David ;

Gattorno, Marco ;

Lanzavecchia, Antonio ;

Sallusto, Federica ;

Napolitani, Giorgio .

NATURE IMMUNOLOGY, 2007, 8 (06) :639-646

[3] Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].

Aggarwal, S ;

Ghilardi, N ;

Xie, MH ;

de Sauvage, FJ ;

Gurney, AL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914

[4] Phenotypic and functional features of human Th17 cells [J].

Annunziato, Francesco ;

Cosmi, Lorenzo ;

Santarlasci, Veronica ;

Maggi, Laura ;

Liotta, Francesco ;

Mazzinghi, Benedetta ;

Parente, Eliana ;

Fili, Lucia ;

Ferri, Simona ;

Frosali, Francesca ;

Giudici, Francesco ;

Romagnani, Paola ;

Parronchi, Paola ;

Tonelli, Francesco ;

Maggi, Enrico ;

Romagnani, Sergio .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1849-1861

[5] Interleukin-1β impairment of transforming growth factor β1 signaling by down-regulation of transforming growth factor β receptor type II and up-regulation of smad7 in human articular Chondrocytes [J].

Bauge, C. ;

Legendre, F. ;

Leclercq, S. ;

Efissalde, J. M. ;

Pujol, J. P. ;

Galera, P. ;

Boumediene, K. .

ARTHRITIS AND RHEUMATISM, 2007, 56 (09) :3020-3032

[6] Autoreactivity by design: Innate B and T lymphocytes [J].

Bendelac, A ;

Bonneville, M ;

Kearney, JF .

NATURE REVIEWS IMMUNOLOGY, 2001, 1 (03) :177-186

[7] Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].

Bettelli, E ;

Carrier, YJ ;

Gao, WD ;

Korn, T ;

Strom, TB ;

Oukka, M ;

Weiner, HL ;

Kuchroo, VK .

NATURE, 2006, 441 (7090) :235-238

[8] Cutting edge: C3, a key component of complement activation, is not required for the development of myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis in mice [J].

Calida, DM ;

Constantinescu, C ;

Purev, E ;

Zhang, GX ;

Ventura, ES ;

Lavi, E ;

Rostami, A .

JOURNAL OF IMMUNOLOGY, 2001, 166 (02) :723-726

[9] Primer:: inflammasomes and interleukin 1β in inflammatory disorders [J].

Church, Leigh D. ;

Cook, Graham P. ;

McDermott, Michael F. .

NATURE CLINICAL PRACTICE RHEUMATOLOGY, 2008, 4 (01) :34-42

[10] Blocking IL-1 in systemic inflammation [J].

Dinarello, CA .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (09) :1355-1359

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