芳基烃受体的激活诱导人源 1 型调节性 T 细胞样和 Foxp3(+)调节性 T 细胞。
Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells.
机构信息
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
出版信息
Nat Immunol. 2010 Sep;11(9):846-53. doi: 10.1038/ni.1915. Epub 2010 Aug 1.
Abstract
The aryl hydrocarbon receptor (AhR) participates in the differentiation of mouse regulatory T cells (T(reg) cells) and interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells), but its role in human T cell differentiation is unknown. We investigated the role of AhR in the differentiation of human induced T(reg) cells (iT(reg) cells). We found that AhR activation promoted the differentiation of CD4(+)Foxp3(-) T cells, which produce IL-10 and control responder T cells through granzyme B. However, activation of AhR in the presence of transforming growth factor-beta1 induced Foxp3(+) iT(reg) cells, which suppress responder T cells through the ectonucleoside triphosphate diphosphohydrolase CD39. The induction of functional Foxp3(+) iT(reg) cells required coordinated action of the transcriptional regulators Smad1 and Aiolos. Thus, AhR is a potential target through which functional iT(reg) cells could be induced in human autoimmune disorders.
摘要
芳香烃受体 (AhR) 参与调节性 T 细胞 (Treg 细胞) 和白细胞介素 17 (IL-17) 产生的辅助性 T 细胞 (T(H)17 细胞) 的分化，但它在人类 T 细胞分化中的作用尚不清楚。我们研究了 AhR 在人诱导性 T 调节细胞 (iTreg 细胞) 分化中的作用。我们发现 AhR 的激活促进了 CD4+Foxp3- T 细胞的分化，这些细胞通过颗粒酶 B 产生 IL-10 并控制应答性 T 细胞。然而，在转化生长因子-β1 存在的情况下激活 AhR 诱导 Foxp3+iTreg 细胞，通过外核苷酸三磷酸二磷酸水解酶 CD39 抑制应答性 T 细胞。功能性 Foxp3+iTreg 细胞的诱导需要转录调节因子 Smad1 和 Aiolos 的协调作用。因此，AhR 是一个潜在的靶点，可以通过它在人类自身免疫性疾病中诱导功能性 iTreg 细胞。
相似文献
1
Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells.
Nat Immunol. 2010 Sep;11(9):846-53. doi: 10.1038/ni.1915. Epub 2010 Aug 1.
2
Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of aryl hydrocarbon receptor.
Invest Ophthalmol Vis Sci. 2010 Apr;51(4):2109-17. doi: 10.1167/iovs.09-3993. Epub 2009 Dec 10.
3
An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis.
Proc Natl Acad Sci U S A. 2010 Nov 30;107(48):20768-73. doi: 10.1073/pnas.1009201107. Epub 2010 Nov 10.
4
Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor.
Nature. 2008 May 1;453(7191):65-71. doi: 10.1038/nature06880. Epub 2008 Mar 23.
5
Tr1 Cells, but Not Foxp3+ Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10-Dependent Mechanism.
J Immunol. 2015 Jul 15;195(2):488-97. doi: 10.4049/jimmunol.1403225. Epub 2015 Jun 8.
6
Activation of the aryl hydrocarbon receptor suppresses sensitization in a mouse peanut allergy model.
Toxicol Sci. 2011 Oct;123(2):491-500. doi: 10.1093/toxsci/kfr175. Epub 2011 Jul 29.
7
Aryl hydrocarbon receptor controls regulatory CD4+ T cell function.
Swiss Med Wkly. 2012 May 31;142:w13592. doi: 10.4414/smw.2012.13592. eCollection 2012.
8
IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells.
Nat Immunol. 2008 Dec;9(12):1347-55. doi: 10.1038/ni.1677. Epub 2008 Nov 9.
9
FICZ generates human tDCs that induce CD4 CD25 Foxp3 Treg-like cell differentiation.
Immunol Lett. 2017 Oct;190:84-92. doi: 10.1016/j.imlet.2017.07.013. Epub 2017 Jul 29.
10
Human adipose-tissue derived mesenchymal stem cells induce functional de-novo regulatory T cells with methylated FOXP3 gene DNA.
Clin Exp Immunol. 2013 Aug;173(2):343-54. doi: 10.1111/cei.12120.
引用本文的文献
1
Slc7a5 promotes T cell anti-tumor immunity through sustaining cytotoxic T lymphocyte effector function.
Oncogene. 2025 Aug 26. doi: 10.1038/s41388-025-03543-5.
2
cGAS-STING pathway as a promising target for digestive diseases: insights from natural plant products.
Front Nutr. 2025 Jun 20;12:1594120. doi: 10.3389/fnut.2025.1594120. eCollection 2025.
3
Physical exercise to rebalance kynurenine metabolism in borderline personality disorder - Preliminary findings.
Brain Behav Immun Health. 2025 Jun 9;47:101030. doi: 10.1016/j.bbih.2025.101030. eCollection 2025 Aug.
4
Microbiota-dependent metabolites - New engine for T cell warriors.
Gut Microbes. 2025 Dec;17(1):2523815. doi: 10.1080/19490976.2025.2523815. Epub 2025 Jun 30.
5
Gut microbiota in regulatory T cell generation and function: mechanisms and health implications.
Gut Microbes. 2025 Dec;17(1):2516702. doi: 10.1080/19490976.2025.2516702. Epub 2025 Jun 15.
6
Harnessing endogenous miRNA targeting ZIKV: A cutting-edge strategy to inhibit virus infection.
Mol Ther Nucleic Acids. 2025 May 14;36(2):102562. doi: 10.1016/j.omtn.2025.102562. eCollection 2025 Jun 10.
7
AhR-Dependent Induction of β-Defensin 1 in Colonic Epithelial Cells Regulates Cross-Talk between Gut Microbiota and Immune Response Leading to Attenuation of Colitis.
Adv Sci (Weinh). 2025 Jul;12(25):e2416324. doi: 10.1002/advs.202416324. Epub 2025 May 23.
8
A probiotic approach identifies a Treg-centred immunoregulation via modulation of gut microbiota metabolites in people with multiple sclerosis and healthy individuals.
EBioMedicine. 2025 Jun;116:105743. doi: 10.1016/j.ebiom.2025.105743. Epub 2025 May 12.
9
Aging immunity: unraveling the complex nexus of diet, gut microbiome, and immune function.
Immunometabolism (Cobham). 2025 May 9;7(2):e00061. doi: 10.1097/IN9.0000000000000061. eCollection 2025 Apr.
10
Efficacy of a postbiotic and its components in promoting colonic transit and alleviating chronic constipation in humans and mice.
Cell Rep Med. 2025 May 20;6(5):102093. doi: 10.1016/j.xcrm.2025.102093. Epub 2025 Apr 25.
本文引用的文献
1
The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27.
Nat Immunol. 2010 Sep;11(9):854-61. doi: 10.1038/ni.1912. Epub 2010 Aug 1.
2
Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+ T cells in pancreatic lymph nodes.
Immunotherapy. 2009 Jul;1(4):539-47. doi: 10.2217/imt.09.24.
3
The regulation of IL-10 production by immune cells.
Nat Rev Immunol. 2010 Mar;10(3):170-81. doi: 10.1038/nri2711. Epub 2010 Feb 15.
4
Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate.
Nature. 2010 Feb 11;463(7282):808-12. doi: 10.1038/nature08750. Epub 2010 Jan 13.
5
Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome.
Immunity. 2009 Dec 18;31(6):932-40. doi: 10.1016/j.immuni.2009.10.006.
6
Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of aryl hydrocarbon receptor.
Invest Ophthalmol Vis Sci. 2010 Apr;51(4):2109-17. doi: 10.1167/iovs.09-3993. Epub 2009 Dec 10.
7
Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells.
Science. 2009 Aug 28;325(5944):1142-6. doi: 10.1126/science.1176077. Epub 2009 Aug 20.
8
Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose.
Immunity. 2009 Aug 21;31(2):209-19. doi: 10.1016/j.immuni.2009.05.012. Epub 2009 Jul 30.
9
Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells.
J Immunol. 2009 Jul 15;183(2):797-801. doi: 10.4049/jimmunol.0901233. Epub 2009 Jul 1.
10
c-Maf regulates IL-10 expression during Th17 polarization.
J Immunol. 2009 May 15;182(10):6226-36. doi: 10.4049/jimmunol.0900123.
Zotero 插件