cDNA cloning and structure of mouse putative Ah receptor

Ema, Masatsugu; Sogawa, Kazuhiro; Watanabe, Nobuaki; Chujoh, Y.; Matsushita, Natsuki; Gotoh, Osamu; Funae, Yoshihiko; Fujii‐Kuriyama, Yoshiaki

doi:10.1016/0006-291x(92)91185-s

Cited by 381 publications

(203 citation statements)

References 23 publications

Supporting

Mentioning

198

Contrasting

Unclassified

Order By: Relevance

“…In situ hybridization was performed as described (Wilkinson 1992) by using cRNA probe synthesized from pBSK vectors carrying AhR cDNA fragments (2141-2839 nt and 2548-3438 nt (Ema et al 1992)). b-galactosidase staining was carried out as described (Gondo et al 1994) with embryos fixed in phosphatebuffered saline (PBS) containing 2% paraformaldehyde, 0.2% glutaraldehyde and 0.05% nonidet P-40.…”

Section: Whole Mount In Situ Hybridization and B-galactosidase Stainingmentioning

confidence: 99%

Loss of teratogenic response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in mice lacking the Ah (dioxin) receptor

et al. 1997

View full text Add to dashboard Cite

Background: The aryl hydrocarbon receptor (AhR or dioxin receptor) is a ligand-activated transcription factor that is considered to mediate pleiotropic biological responses such as teratogenesis, tumour promotion, epithelial hyperplasia and the induction of drug-metabolizing enzymes to environmental contaminants usually represented by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In contrast to the role of AhR in the regulatory mechanism of xenobiotic-metabolizing enzymes, there is no direct proof that the AhR is involved in the teratogenic effects of TCDD.

show abstract

Section: Whole Mount In Situ Hybridization and B-galactosidase Stainingmentioning

confidence: 99%

Loss of teratogenic response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in mice lacking the Ah (dioxin) receptor

et al. 1997

View full text Add to dashboard Cite

show abstract

“…In this paper, we demonstrate that Ahr is involved in the differentiation of Th17 cells by regulating Stat1 activation, which suppresses Th17 cell differentiation, under Th17-polarizing conditions. Ahr, also known as dioxin receptor, is a ligand-activated transcription factor that belongs to the basic-helix-loop-helix-PER-ARNT-SIM family (12,13). Ahr is present in the cytoplasm, where it forms a complex with heat shock protein (HSP) 90, Ahr-interacting protein (AIP), and p23 (14-16).…”

mentioning

confidence: 99%

Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells

Kimura

Naka

Nohara

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

456

418

View full text Add to dashboard Cite

IL-17-producing T helper cells (Th17) have been recently identified as a previously undescribed subset of helper T cells. Here, we demonstrate that aryl hydrocarbon receptor (Ahr) has an important regulatory function in the commitment of Th17 cells. Ahr was robustly induced under Th17-polarizing conditions. Ahr-deficient naïve T cells showed a considerable loss in the ability to differentiate into Th17 cells when induced by TGF-␤ plus IL-6. We were able to demonstrate that Ahr interacts with Stat1 and Stat5, which negatively regulate Th17 development. Whereas Stat1 activation returned to its basal level in Ahr wild type naïve T cells 24 h after stimulation with TGF-␤ plus IL-6, Stat1 remained activated in Ahr-deficient naïve T cells after stimulation. These results indicate that Ahr participates in Th17 cell differentiation through regulating Stat1 activation, a finding that constitutes additional mechanisms in the modulation of Th17 cell development. It has been demonstrated that these Th17 cells are associated with autoimmune conditions, such as experimental autoimmune encephalitis (EAE) and collagen-induced arthritis (CIA) (1-3). Th17 differentiation is regulated by various cytokines. Th17 differentiation was induced by TGF-␤ and IL-6 in mice, and IL-1␤ but not TGF-␤, has been shown to participate in the development of Th17 cells together with IL-6 in humans (2, 4). The development of Th17 cells is regulated negatively by IFN-␥, IL-27, and IL-2, the signals of which are dependent on Stat1 (IFN-␥ and IL-27) and Stat5 (IL-2), respectively (5-7). The orphan nuclear receptors, retinoid-related orphan receptor ␥ (ROR␥) and ROR␣, have been identified as the key transcription factors that determine the differentiation of Th17 lineage (8, 9). More recently, two groups have reported that the aryl hydrocarbon receptor (Ahr) activated by its ligand regulates Treg and Th17 cell development (10, 11). However, it is not clear how Ahr participates in the development of Th17 cells. In this paper, we demonstrate that Ahr is involved in the differentiation of Th17 cells by regulating Stat1 activation, which suppresses Th17 cell differentiation, under Th17-polarizing conditions. Ahr, also known as dioxin receptor, is a ligand-activated transcription factor that belongs to the basic-helix-loop-helix-PER-ARNT-SIM family (12,13). Ahr is present in the cytoplasm, where it forms a complex with heat shock protein (HSP) 90, Ahr-interacting protein (AIP), and p23 (14-16). Upon binding with a ligand, Ahr undergoes a conformation change, translocates to the nucleus, and dimerizes with Ahr nuclear translocator (Arnt). Within the nucleus, the Ahr/Arnt heterodimer binds to a specific sequence, designated as the xenobiotic responsive element (XRE), which causes a variety of toxicological effects (17)(18)(19)(20). Interestingly, it has been recently reported that Ahr is a ligand-dependent E3 ubiquitin ligase (21), implying that Ahr has dual functions in controlling intracellular protein levels, serving both as a transcriptional factor to prom...

show abstract

“…AHR is a ligand-activated transcription factor that belongs to the basic helix-loop-helix (bHLH)/PER-ARNT-SIM (PAS) family (26)(27)(28). Since the original finding that AHR regulates the balance of regulatory T (T reg ) and T H 17 cells (5-7), evidence for the role of AHR in immune regulation has continued to accumulate.…”

mentioning

confidence: 99%

Aryl hydrocarbon receptor-mediated induction of the microRNA-132/212 cluster promotes interleukin-17–producing T-helper cell differentiation

Nakahama

Hanieh

Nguyen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

121

102

View full text Add to dashboard Cite

Aryl hydrocarbon receptor (AHR) plays critical roles in various autoimmune diseases such as multiple sclerosis by controlling interleukin-17 (IL-17)-producing T-helper (T H 17) and regulatory T cells. Although various transcription factors and cytokines have been identified as key participants in T H 17 generation, the role of microRNAs in this process is poorly understood. In this study, we found that expression of the microRNA (miR)-132/212 cluster is upregulated by AHR activation under T H 17-inducing, but not regulatory T-inducing conditions. Deficiency of the miR-132/212 cluster prevented the enhancement of T H 17 differentiation by AHR activation. We also identified B-cell lymphoma 6, a negative regulator of T H 17 differentiation, as a potential target of the miR-212. Finally, we investigated the roles of the miR-132/212 cluster in experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. Mice deficient in the miR-132/212 cluster exhibited significantly higher resistance to the development of experimental autoimmune encephalomyelitis and lower frequencies of both T H 1 and T H 17 cells in draining lymph nodes. Our findings reveal a unique mechanism of AHR-dependent T H 17 differentiation that depends on the miR-132/212 cluster. dioxin receptor | autoimmunity | immune regulation

show abstract

cDNA cloning and structure of mouse putative Ah receptor

Cited by 381 publications

References 23 publications

Loss of teratogenic response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in mice lacking the Ah (dioxin) receptor

Loss of teratogenic response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in mice lacking the Ah (dioxin) receptor

Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells

Aryl hydrocarbon receptor-mediated induction of the microRNA-132/212 cluster promotes interleukin-17–producing T-helper cell differentiation

Contact Info

Product

Resources

About