Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor

被引：0
作者：
Francisco J. Quintana
Alexandre S. Basso
Antonio H. Iglesias
Thomas Korn
Mauricio F. Farez
Estelle Bettelli
Mario Caccamo
Mohamed Oukka
Howard L. Weiner
机构：
[1] Center for Neurologic Diseases,
[2] Brigham and Women’s Hospital,undefined
[3] Harvard Medical School,undefined
[4] 77 Avenue Louis Pasteur,undefined
[5] Boston,undefined
[6] Massachusetts 02115,undefined
[7] USA ,undefined
[8] EMBL Outstation – Hinxton,undefined
[9] European Bioinformatics Institute,undefined
[10] Wellcome Trust Genome Campus,undefined
[11] Hinxton,undefined
[12] Cambridge CB10 1SD,undefined
[13] UK ,undefined
[14] Center for Neurologic Diseases,undefined
[15] Brigham and Women’s Hospital,undefined
[16] Harvard Medical School,undefined
[17] 65 Landsdowne Street,undefined
[18] Cambridge,undefined
[19] Massachusetts 02139,undefined
[20] USA ,undefined
来源：
Nature | 2008年 / 453卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Regulatory T cells (Treg) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of Treg cells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (TH17). Although Treg cell dysfunction and/or TH17 cell dysregulation are thought to contribute to the development of autoimmune disorders, little is known about the physiological pathways that control the generation of these cell lineages. Here we report the identification of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) as a regulator of Treg and TH17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional Treg cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with Treg cell development, boosted TH17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both Treg and TH17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation.
引用
收藏
页码：65 / 71
页数：6
相关论文
共 79 条
[1]  
Sakaguchi S(2004)Naturally arising CD4 Annu. Rev. Immunol. 22 531-562
[2]  
Fontenot JD(2003) regulatory T cells for immunologic self-tolerance and negative control of immune responses Nature Immunol. 4 330-336
[3]  
Gavin MA(2003)Foxp3 programs the development and function of CD4 Science 299 1057-1061
[4]  
Rudensky AY(2001)CD25 Nature Genet. 27 68-73
[5]  
Hori S(2000) regulatory T cells J. Clin. Invest. 106 R75-R81
[6]  
Nomura T(2006)Control of regulatory T cell development by the transcription factor Foxp3 Proc. Natl Acad. Sci. USA 103 6659-6664
[7]  
Sakaguchi S(2003)Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse J. Exp. Med. 198 1875-1886
[8]  
Brunkow ME(2006)JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome Immunity 24 179-189
[9]  
Chatila TA(2007)Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development Nature 448 484-487
[10]  
Gavin MA(2006)Conversion of peripheral CD4 Cell 126 1121-1133
12345678