Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3
            <sup>+</sup>
            regulatory T cells

Wei, Jun; Duramad, Omar; Perng, Olivia A.; Reiner, Steven L.; Liu, Yong Jun; Qin, F. Xiao-Feng

doi:10.1073/pnas.0703642104

Cited by 217 publications

(247 citation statements)

References 33 publications

Supporting

Mentioning

210

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have reported that murine FoxP3 interacts with GATA3 (11,30). Here, we confirmed the interaction between human FOXP3 and GATA3 by co-immunoprecipitation (Fig.…”

Section: Foxp3 Gata3 and Usp21 Forms A Positive Feedback Loop-supporting

confidence: 76%

See 1 more Smart Citation

Identification of the E3 Deubiquitinase Ubiquitin-specific Peptidase 21 (USP21) as a Positive Regulator of the Transcription Factor GATA3

Zhang

Chen

Hou³

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Previous studies have reported that murine FoxP3 interacts with GATA3 (11,30). Here, we confirmed the interaction between human FOXP3 and GATA3 by co-immunoprecipitation (Fig.…”

Section: Foxp3 Gata3 and Usp21 Forms A Positive Feedback Loop-supporting

confidence: 76%

“…GATA3 can interact with FOXP3 (10,11). In Treg cells, FOXP3 interacts with GATA3 to inhibit the expression of the Th-2 cytokines IL-4, IL-5, and IL-13 (12); but unlike GATA3 expression during Th2 polarization, the expression of GATA3 in nTreg cells is independent of STAT6 signaling (5).…”

Section: Important Signaling Loop That Stabilizes the Expression Of Gmentioning

confidence: 99%

Identification of the E3 Deubiquitinase Ubiquitin-specific Peptidase 21 (USP21) as a Positive Regulator of the Transcription Factor GATA3

Zhang

Chen

Hou³

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It has been reported that Treg differentiation is negatively regulated by IFN-␥ in a Stat1-dependent manner (28). We confirmed that IFN-␥ partially inhibits Treg cell development by TGF-␤ and that IFN-␥ blocking by its neutralizing antibodies enhances Treg differentiation (Fig.…”

Section: Il-17 Is Produced In Cd4 ؉ Cd62l ؊ Cells Without Tgf-␤ Plus supporting

confidence: 76%

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.

448

410

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

“…It is critically involved in the initiation of Th1 inflammatory cascade (18)(19)(20)(21)(22). Activation of STAT1 promotes the activation of dentritic cells (DCs) (22,23) and natural killer (NK) cells (24), and inhibits the development of regulatory T cells (25,26). pSTAT3, which has antagonistic effect on pSTAT1 (27,28), is not only a potent negative regulator of the Th1-mediated inflammatory response, but also an activator of many genes that are crucial for immune regulation (29,30).…”

Section: Introductionmentioning

confidence: 99%

Dynamic Balance of pSTAT1 and pSTAT3 in C57BL/6 Mice Infected with Lethal Or Nonlethal Plasmodium yoelii

Shi

Liu

et al. 2008

Cell Mol Immunol

View full text Add to dashboard Cite

Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3 ⁺ regulatory T cells

Abstract: T cell differentiation ͉ T cell tolerance ͉ cell fate determination ͉ transcriptional regulation ͉ cytokine signaling

Cited by 217 publications

References 33 publications

Identification of the E3 Deubiquitinase Ubiquitin-specific Peptidase 21 (USP21) as a Positive Regulator of the Transcription Factor GATA3

Identification of the E3 Deubiquitinase Ubiquitin-specific Peptidase 21 (USP21) as a Positive Regulator of the Transcription Factor GATA3

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

Dynamic Balance of pSTAT1 and pSTAT3 in C57BL/6 Mice Infected with Lethal Or Nonlethal Plasmodium yoelii

Contact Info

Product

Resources

About

Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3 + regulatory T cells

Abstract: T cell differentiation ͉ T cell tolerance ͉ cell fate determination ͉ transcriptional regulation ͉ cytokine signaling

Cited by 217 publications

References 33 publications

Identification of the E3 Deubiquitinase Ubiquitin-specific Peptidase 21 (USP21) as a Positive Regulator of the Transcription Factor GATA3

Identification of the E3 Deubiquitinase Ubiquitin-specific Peptidase 21 (USP21) as a Positive Regulator of the Transcription Factor GATA3

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

Dynamic Balance of pSTAT1 and pSTAT3 in C57BL/6 Mice Infected with Lethal Or Nonlethal Plasmodium yoelii

Contact Info

Product

Resources

About

Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3 ⁺ regulatory T cells