Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor
Abstract
Regulatory T cells (T(reg)) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of T(reg) cells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (T(H)17). Although T(reg) cell dysfunction and/or T(H)17 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 T(reg) and T(H)17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional T(reg) cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with T(reg) cell development, boosted T(H)17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both T(reg) and T(H)17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation.
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Many phenotypes of Ahr mutant models, such as altered hepatovascular development and impaired immune function, do not appear to be directly related to TCDD toxicity or adaptive metabolism.
“Accordingly, many phenotypes of Ahr mutant models such as altered hepatovascular development and impaired immune function, do not appear to be directly related to TCDD toxicity or adaptive metabolism (Quintana et al., 2008; Stockinger et al., 2014; Veldhoen et al., 2008; Walisser et al., 2005)”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Quintana et al., 2008
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References 41 · Cited by 1,865
- Authors
- Quintana, F. J., Basso, A. S., Iglesias, A. H., Korn, T., Farez, M. F., Bettelli, E., Caccamo, M., Oukka, M., & Weiner, H. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Weiner, Howard L.
- ORCID
- Venue
- Nature
- Published
- 2008-03-23
- Volume
- 453
- Issue
- 7191
- Pages
- 65-71
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2004522121
- Cited by
- 1,865
- References
- 41
- Citations by year
- 2026: 68 · 2025: 88 · 2024: 91 · 2023: 93 · 2022: 120 · 2021: 108 · 2020: 128 · 2019: 95 · 2018: 108 · 2017: 98 · 2016: 99 · 2015: 100 · 2014: 100 · 2013: 109 · 2012: 117
- FWCI
- 47.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI073542, AI435801)
- National Institute of Neurological Disorders and Stroke (NS 38037, P01NS038037, R01NS059996)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- aryl hydrocarbon receptor, regulatory T cells, Th17 cells, Foxp3, Treg differentiation, Th17 cell differentiation, experimental autoimmune encephalomyelitis, multiple sclerosis, 2,3,7,8-tetrachlorodibenzo-p-dioxin, FICZ, immunomodulation, autoimmune disease, environmental pollutants, transcription factors
- MeSH terms
- Polychlorinated Dibenzodioxins, Animals, Carbazoles, Cell Differentiation, Encephalomyelitis, Autoimmune, Experimental, T-Lymphocytes, Helper-Inducer, Humans, Indoles, Ligands, Mice, Inbred C57BL, Receptors, Aryl Hydrocarbon, Interleukin-17, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Transforming Growth Factor beta1
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