Reciprocal TH17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid

  title={Reciprocal TH17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid},
  author={Daniel Mucida and Yunji Park and Gisen Kim and O. V. Turovskaya and Iain Scott and Mitchell Kronenberg and Hilde Cheroutre},
  pages={256 - 260}
The cytokine transforming growth factor–β (TGF-β) converts naïve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-β has also been found to promote the differentiation of naïve T lymphocytes into proinflammatory IL-17 cytokine-producing T helper 17 (TH17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-β can generate such distinct outcomes. We identified the vitamin A metabolite… 

TGFβ and Retinoic Acid Intersect in Immune-Regulation

A vitamin A metabolite, retinoic acid, was recently identified as a key modulator of TGFβ-driven immune deviation capable of suppressing TH17 differentiation while promoting Foxp3+Treg generation 6-10 and suggests that a sensitive regulatory mechanism must exist to control TGF β-driven TH17 effector and Treg differentiation.

Retinoic acid in mucosal immune-regulation

RA is described as a key modulator of TGF-β-driven immune deviation capable of suppressing TH17 differentiation while promoting Foxp3+ Treg generation and how RA can affect mucosal immune regulation is discussed.

Transcriptional regulation of Th17 cell differentiation.

Regulatory T cells: Reciprocal regulation by retinoic acid

  • O. Leavy
  • Biology, Medicine
    Nature Reviews Immunology
  • 2007
It is shown that the vitamin A metabolite retinoic acid is a key regulator of TGFβ-induced T-cell differentiation and has important implications for the understanding of vitamin A deficiency and highlights the therapeutic potential of retinosic acid in diseases in which there is an imbalance in the numbers of T GFβ-dependent TH17 cells and regulatory T cells.

IL-6: A Pleiotropic Cytokine and T H 17 Cells

The recent progress in the field of TH17 cell differentiation and regulation is reviewed and the critical functions of IL-6 and TH17 in immunity and diseases are described.

Th17 cells: The emerging reciprocal partner of regulatory T cells in the liver

It is proposed that the fine balance between Th17 and Treg cells is crucial for maintenance of immune homeostasis and may provide an opportunity to illustrate the pathogenesis of hepatic inflammation and to explore new therapeutic targets for immune‐related liver diseases.

TGFβ1 and Treg cells: alliance for tolerance

TGF-β function in immune suppression.

Recent studies suggest that Smad2 as well as Smad3 play essential roles in Foxp3 induction and cytokine suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway.

Th17 cells in inflammation.




Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells

It is shown that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β, and the data demonstrate a dichotomy in thegeneration of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T Cells that inhibit autoimmune tissue injury.

Transforming growth factor-β induces development of the TH17 lineage

Transforming growth factor-β (TGF-β) is identified as a cytokine critical for commitment to TH17 development and provides a mechanism for divergence of the TH1, TH2 and TH17 lineages.

Control of Regulatory T Cell Development by the Transcription Factor Foxp3

Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.

Cutting Edge: IL-2 Is Essential for TGF-β-Mediated Induction of Foxp3+ T Regulatory Cells

TGF-β is a pluripotent cytokine that is capable of inducing the expression of Foxp3 in naive T lymphocytes and may prove useful for the treatment of autoimmune diseases, for the prevention of graft rejection, and graft versus host disease.

Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation

The major regulatory pathways, including transforming growth factor‐β (TGF‐β), interleukin‐10 (IL‐10), and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), and their role in Treg‐mediated control of systemic and mucosal responses are discussed.