TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology

@article{McGeachy2007TGFAI,
  title={TGF-$\beta$ and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology},
  author={Mandy J. McGeachy and Kristian Sass Bak-Jensen and Yi Chen and Cristina M Tato and Wendy M. Blumenschein and Terrill K. Mcclanahan and Daniel J. Cua},
  journal={Nature Immunology},
  year={2007},
  volume={8},
  pages={1390-1397}
}
Studies have shown that transforming growth factor-β (TGF-β) and interleukin 6 (IL-6) are required for the lineage commitment of pathogenic IL-17-producing T helper cells (TH-17 cells. [] Key Result Cells stimulated with TGF-β plus IL-6 were present in the spleen as well as the central nervous system, but they failed to upregulate the proinflammatory chemokines crucial for central nervous system inflammation. In addition, these cells produced IL-10, which has potent anti-inflammatory activities.
The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt
TLDR
These studies identify RORγt as having a central function in the differentiation of human TH-17 cells from naive CD4+ T cells and suggest that similar cytokine pathways are involved in this process in mice and humans.
Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in TH17 cells
TLDR
It is found that c-Maf bound to the Il22 promoter and was both necessary and sufficient for the TGF-β-dependent suppression of IL-22 production in TH17 cells.
A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses
TLDR
It is shown here that transforming growth factor-β, interleukin 23 (IL-23) and proinflammatory cytokines ( IL-1β and IL-6) were all essential for human TH-17 differentiation and provide a framework for the global analysis of T helper responses.
Generation of Pathogenic Th17 Cells in the Absence of TGF-β Signaling
TLDR
It is shown that TH17 differentiation can occur in the absence of TGF-β signalling, and this findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications.
Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β
TLDR
These findings demonstrate that by eliciting different cytokines C. albicans and S. aureus prime TH17 cells that produce either IFN-γ or IL-10, and identify IL-1β and IL-2 as pro- and anti-inflammatory regulators of TH17 Cells both at priming and in the effector phase.
Late developmental plasticity in the T helper 17 lineage.
The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF
TLDR
Cross-regulation of IL-23 and GM- CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies TH17 cells as a crucial source of GM-CSF in autoimmune inflammation.
TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
TLDR
It is shown that a population of IL-17 + IL-22 + , but not single IL- 22 + , CD4 + T cells are induced by TGF-β, enriched in patients with colorectal cancer (CRC) and drive CRC progression in mice.
Interleukin-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of interleukin-22, but not interleukin-21, in autoimmune experimental arthritis.
TLDR
IL-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of IL-22, but not IL-21, levels in autoimmune arthritis, which indicate different mechanisms for IL-23 and TGFbeta1/IL-6 at the transcription factor level during Th 17 differentiation in autoimmune experimental arthritis.
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TLDR
IL-6 orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-β, amplify RORγt-dependent differentiation of TH-17 cells.
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IL-22 is identified as a new cytokine expressed by Th17 cells that synergizes with IL- 17A or IL-17F to regulate genes associated with skin innate immunity.
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TLDR
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TLDR
The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation.
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