<i>Fine-tuning innate and adaptive immune responses: another KLFhanger</i>. Focus on “Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8<sup>+</sup> T lymphocytes”

Feinberg, Mark W.

doi:10.1152/ajpcell.00418.2014

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…There are cross talks between AhR and TGF-β pathway in anti-inflammatory processes demonstrated in mammals [57][58][59]. A direct evidence of AhR/TGF-β/Smad pathway in an anti-inflammation context was demonstrated lately in scurfy mice, a mouse model of immunodysregulation polyendocrinopathy enteropathy X-linked syndrome, in which ligand activated AhR-TGF-β/Smad signaling mediates autoimmune suppression [40,46]. The current findings that AhR signaling connects chemical sensing and immune regulation in mosquitoes warrant further study to elucidate the cross talk between xenobiotic defense and immune defense in insect level.…”

Section: Discussionmentioning

confidence: 99%

“…One of the AhR dependent genes, AGAP009889, encodes a transcription factor in the Sp1like/Krüppel-like family [40], which is a ortholog of the vertebrate TGF-β-inducible earlyresponse gene (TIEG) [41]. The orthologous gene in Drosophila is Cabut, which is involved in development, metabolism and growth control [42][43][44][45].…”

Section: Ahr -Tieg Axis Mediates a Negative Immune Modulationmentioning

confidence: 99%

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Aryl hydrocarbon receptor and TGF-β inducible early gene mediate a transcriptional axis modulating immune homeostasis in mosquitoes

Kulkarni

Pandey

Trainor

et al. 2020

Preprint

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Immune homeostasis balances effective defense against pathogens with avoiding the adverse effect of immune overactivation. AhR is a ligand activated transcription factor that transduces chemical signals into transcription of a variety of target genes. In this study, we demonstrate that mosquito AhR and TIEG mediate a transcriptional axis modulating immune response negatively. When AhR was activated by diet delivery of agonist kynurenine, the anti-bacterial immunity was compromised with a reduced survival at 24hr post bacterial challenge. In contrast, when AhR was inhibited by antagonists, CH223191 or SR1, the immunity was enhanced with increased survival. The observed immune enhancement via AhR antagonist was corroborated by AhR gene silencing via RNAi, which resulted in increased survival upon the infection. Exploration of transcriptomes following AhR inactivation, either pharmacologically or genetically, highlighted a set of genes that are infection inducible and AhR dependent, including genes that may mediate immune suppressive functions. One of the genes, TIEG (TGF-β inducible early gene), a member of the Krüppel-like factor family of transcription factors, was further studied. TIEG is required for AhR mediated immune suppression. Silencing TIEG increased the survival and reversed the immune suppression mediated by kynurenine activation of AhR. Moreover, the mosquito cohorts with AhR or TIEG knockdown demonstrated similar transcriptomic responses upon infection. There were co-expression patterns shared between the respective cohorts treated with AhR antagonist or AhR and TIEG silencing. In the naïve mosquitoes where the IMD pathway was overactivated by silencing the inhibitor gene Caspar, co-silencing Caspar with AhR or TIEG resulted in a reduced survival, indicating the AhR-TIEG axis is required to prevent the adverse effect of over-activation of IMD without an infection. Together, AhR and TIEG are involved in a transcriptional axis that is critical for maintaining immune homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Ahr -Tieg Axis Mediates a Negative Immune Modulationmentioning

confidence: 99%

Aryl hydrocarbon receptor and TGF-β inducible early gene mediate a transcriptional axis modulating immune homeostasis in mosquitoes

Kulkarni

Pandey

Trainor

et al. 2020

Preprint

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Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8⁺ T lymphocytes

Papadakis

Krempski

Reiter

et al. 2015

American Journal of Physiology-Cell Physiology

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KLF10 has recently elicited significant attention as a transcriptional regulator of transforming growth factor-β1 (TGF-β1) signaling in CD4+ T cells. In the current study, we demonstrate a novel role for KLF10 in the regulation of TGF-β receptor II (TGF-βRII) expression with functional relevance in antiviral immune response. Specifically, we show that KLF10-deficient mice have an increased number of effector/memory CD8+ T cells, display higher levels of the T helper type 1 cell-associated transcription factor T-bet, and produce more IFN-γ following in vitro stimulation. In addition, KLF10−/− CD8+ T cells show enhanced proliferation in vitro and homeostatic proliferation in vivo. Freshly isolated CD8+ T cells from the spleen of adult mice express lower levels of surface TGF-βRII (TβRII). Congruently, in vitro activation of KLF10-deficient CD8+ T cells upregulate TGF-βRII to a lesser extent compared with wild-type (WT) CD8+ T cells, which results in attenuated Smad2 phosphorylation following TGF-β1 stimulation compared with WT CD8+ T cells. Moreover, we demonstrate that KLF10 directly binds to the TGF-βRII promoter in T cells, leading to enhanced gene expression. In vivo viral infection with Daniel's strain Theiler's murine encephalomyelitis virus (TMEV) also led to lower expression of TGF-βRII among viral-specific KLF10−/− CD8+ T cells and a higher percentage of IFN-γ-producing CD8+ T cells in the spleen. Collectively, our data reveal a critical role for KLF10 in the transcriptional activation of TGF-βRII in CD8+ T cells. Thus, KLF10 regulation of TGF-βRII in this cell subset may likely play a critical role in viral and tumor immune responses for which the integrity of the TGF-β1/TGF-βRII signaling pathway is crucial.

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Fine-tuning innate and adaptive immune responses: another KLFhanger. Focus on “Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8⁺ T lymphocytes”

Cited by 2 publications

References 9 publications

Aryl hydrocarbon receptor and TGF-β inducible early gene mediate a transcriptional axis modulating immune homeostasis in mosquitoes

Aryl hydrocarbon receptor and TGF-β inducible early gene mediate a transcriptional axis modulating immune homeostasis in mosquitoes

Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8⁺ T lymphocytes

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Fine-tuning innate and adaptive immune responses: another KLFhanger. Focus on “Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes”

Cited by 2 publications

References 9 publications

Aryl hydrocarbon receptor and TGF-β inducible early gene mediate a transcriptional axis modulating immune homeostasis in mosquitoes

Aryl hydrocarbon receptor and TGF-β inducible early gene mediate a transcriptional axis modulating immune homeostasis in mosquitoes

Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes

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Fine-tuning innate and adaptive immune responses: another KLFhanger. Focus on “Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8⁺ T lymphocytes”

Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8⁺ T lymphocytes