The Cytokines Interleukin 27 and Interferon-γ Promote Distinct Treg Cell Populations Required to Limit Infection-Induced Pathology

被引:290
作者
Hall, Aisling O'Hara [1 ]
Beiting, Daniel P. [2 ]
Tato, Cristina [3 ]
John, Beena [1 ]
Oldenhove, Guillaume [5 ]
Lombana, Claudia Gonzalez [1 ]
Pritchard, Gretchen Harms [1 ]
Silver, Jonathan S. [1 ]
Bouladoux, Nicolas [5 ]
Stumhofer, Jason S. [1 ]
Harris, Tajie H. [1 ]
Grainger, John [5 ]
Wojno, Ella D. Tait [1 ]
Wagage, Sagie [1 ]
Roos, David S. [2 ]
Scott, Philip [1 ]
Turka, Laurence A. [6 ]
Cherry, Sara [2 ]
Reiner, Steven L. [4 ]
Cua, Daniel [2 ]
Belkaid, Yasmine [3 ]
Elloso, M. Merle
Hunter, Christopher A. [1 ]
机构
[1] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA
[2] Univ Penn, Penn Genome Frontiers Inst, Dept Biol, Philadelphia, PA 19104 USA
[3] DNAX Discovery Res, Merck Res Labs, Palo Alto, CA 94304 USA
[4] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[5] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
[6] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Inst, Boston, MA 02215 USA
关键词
REGULATORY T-CELLS; IFN-GAMMA; EXPRESSION; BET; INDUCTION; HOMEOSTASIS; ACTIVATION; DEPLETION; RESPONSES; EFFECTOR;
D O I
10.1016/j.immuni.2012.06.014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interferon-gamma (IFN-gamma) promotes a population of T-bet(+) CXCR3(+) regulatory T (Treg) cells that limit T helper 1 (Th1) cell-mediated pathology. Our studies demonstrate that interleukin-27 (IL-27) also promoted expression of T-bet and CXCR3 in Treg cells. During infection with Toxoplasma gondii, a similar population emerged that limited T cell responses and was dependent on IFN-gamma in the periphery but on IL-27 at mucosa! sites. Transfer of Treg cells ameliorated the infection-induced pathology observed in Il27(-/-) mice, and this was dependent on their ability to produce IL-10. Microarray analysis revealed that Treg cells exposed to either IFN-gamma or IL-27 have distinct transcriptional profiles. Thus, IFN-gamma and IL-27 have different roles in Treg cell biology and IL-27 is a key cytokine that promotes the development of Treg cells specialized to control Th1 cell-mediated immunity at local sites of inflammation.
引用
收藏
页码:511 / 523
页数:13
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