Cutting edge: IL-27 is a potent inducer of IL-10 but not FoxP3 in murine T cells

被引:177
作者
Batten, Marcel [1 ]
Kljavin, Noelyn M. [1 ]
Li, Ji [1 ]
Walter, Michael J. [2 ]
de Sauvage, Frederic J. [1 ]
Ghilardi, Nico [1 ]
机构
[1] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA
[2] Washington Univ, Sch Med Pulm & Crit Care Med, St Louis, MO 63110 USA
关键词
D O I
10.4049/jimmunol.180.5.2752
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The cytokine IL-27 is important for restricting inflammation in response to a wide variety of immune challenges. In this study, we demonstrate that IL-27 induces expression of the anti-inflammatory cytokine IL-10 by CD4(+) and CD8(+) T cells. IL-27 relied upon the Th1 transcription factor STAT1 to induce IL-10(+)IFN-gamma(+)FoxP3(-) Th1 cells, which were recently shown to be key negative regulators during certain infections. IL27ra(-/-) mice generated fewer IL-10(+) T cells during both Listeria monocytogenes infection and experimental autoimmune encephalomyelitis. The data presented here indicate a novel mechanism for the induction of IL-10 expression by T cells and provide a mechanistic basis for the suppressive effects of IL-27.
引用
收藏
页码:2752 / 2756
页数:5
相关论文
共 30 条
[1]   CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis [J].
Anderson, Charles F. ;
Oukka, Mohammed ;
Kuchroo, Vijay J. ;
Sacks, David .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (02) :285-297
[2]   The biology and therapeutic potential of interleukin 27 [J].
Batten, Marcel ;
Ghilardi, Nico .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2007, 85 (07) :661-672
[3]   Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells [J].
Batten, Marcel ;
Li, Ji ;
Yi, Sothy ;
Kljavin, Noelyn M. ;
Danilenko, Dimitry M. ;
Lucas, Sophie ;
Lee, James ;
de Sauvage, Frederic J. ;
Ghilardi, Nico .
NATURE IMMUNOLOGY, 2006, 7 (09) :929-936
[4]   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
[5]   Development of Th1-type immune responses requires the type I cytokine receptor TCCR [J].
Chen, Q ;
Ghilardi, N ;
Wang, H ;
Baker, T ;
Xie, MH ;
Gurney, A ;
Grewal, IS ;
de Sauvage, FJ .
NATURE, 2000, 407 (6806) :916-920
[6]   Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis [J].
Cua, DJ ;
Hutchins, B ;
LaFace, DM ;
Stohlman, SA ;
Coffman, RL .
JOURNAL OF IMMUNOLOGY, 2001, 166 (01) :602-608
[7]  
Daftarian PM, 1996, J IMMUNOL, V157, P12
[8]   Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells [J].
Fitzgerald, Denise C. ;
Zhang, Guang-Xian ;
El-Behi, Mohamed ;
Fonseca-Kelly, Zoe ;
Li, Hongmei ;
Yu, Shuo ;
Saris, Christiaan J. M. ;
Gran, Bruno ;
Ciric, Bogoljub ;
Rostami, Abdolmohamad .
NATURE IMMUNOLOGY, 2007, 8 (12) :1372-U6
[9]   Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10 [J].
Gerosa, F ;
Paganin, C ;
Peritt, D ;
Paiola, F ;
Scupoli, MT ;
AsteAmezaga, M ;
Frank, I ;
Trinchieri, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (06) :2559-2569
[10]   Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma [J].
Hawrylowicz, CM ;
O'Garra, A .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (04) :271-283