Cutting Edge: Alternative Signaling of Th17 Cell Development by Sphingosine 1-Phosphate

Liao, Jia‐Jun; Huang, Mei‐Chuan; Goetzl, Edward J.

doi:10.4049/jimmunol.178.9.5425

Cited by 111 publications

(96 citation statements)

References 29 publications

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“…DCs prepared from monocytes exposed to GM-CSF and IL-4, as described in most other studies (26, 30 -32), appear to behave differently than do those that mature in the absence of IL-4. Notably, IL-4 has been implicated in Th17 inhibition in some murine studies (8,33,34). To determine the degree to which IL-4 influences IL-23 production by human monocyte-derived DCs, we compared culture with and without IL-4 (Fig.…”

Section: Il-4 Inhibits Il-23 Production By Single Tlr Agonist-treatedmentioning

confidence: 99%

Differential Production of IL-23 and IL-12 by Myeloid-Derived Dendritic Cells in Response to TLR Agonists

Roses

et al. 2008

The Journal of Immunology

103

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The recently delineated role for IL-23 in enhancing Th-17 activity suggests that regulation of its expression is distinct from that of IL-12. We hypothesized that independent TLR-mediated pathways are involved in the regulation of IL-12 and IL-23 production by myeloid-derived dendritic cells (DCs). The TLR 2 ligand, lipoteichoic acid (LTA), the TLR 4 ligand, LPS, and the TLR 7/8 ligand, resimiquod (R848), induced production of IL-23 by DCs. None of these TLR ligands alone induced significant IL-12 production, except when combined with IFN-γ or other TLR ligands. Notably, IL-23 production in response to single TLR ligands was inhibited by IL-4. DCs treated with single TLR agonists induced IL-17A production by allogeneic and Ag-specific memory CD4+ T cells, an effect that was abrogated by IL-23 neutralization. Moreover, these DCs stimulated IL-17A production by tumor peptide-specific CD8+ T cells. In contrast, DCs treated with dual signals induced naive and memory Th1 responses and enhanced the functional avidity of tumor-specific CD8+ T cells. These results indicate that distinct microbial-derived stimuli are required to drive myeloid DC commitment to IL-12 or IL-23 production, thereby differentially polarizing T cell responses.

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Section: Il-4 Inhibits Il-23 Production By Single Tlr Agonist-treatedmentioning

confidence: 99%

Differential Production of IL-23 and IL-12 by Myeloid-Derived Dendritic Cells in Response to TLR Agonists

Roses

et al. 2008

The Journal of Immunology

103

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“…Elevated levels of S1P and S1P 1 have been demonstrated in the synovium of patients with rheumatoid arthritis (9,10), and S1P signaling through S1P 1 was also found to promote synoviocyte proliferation (10) and inflammatory cytokine-induced cyclooxygenase-2 and PGE 2 production (10). Furthermore, S1P 1 signaling has been shown to augment Th17 differentiation, one of the major T cell populations involved in autoimmune diseases (11,12).…”

mentioning

confidence: 99%

Amelioration of Collagen-Induced Arthritis by a Novel S1P1 Antagonist with Immunomodulatory Activities

Fujii

Hirayama

Ohtake

et al. 2012

The Journal of Immunology

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Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking through the type 1 sphingosine 1-phosphate receptor (S1P1) and participates in many pathological conditions, including autoimmune diseases. We developed a novel S1P1-selective antagonist, TASP0277308, which is structurally unrelated to S1P. This antagonist competitively inhibited S1P-induced cellular responses, such as chemotaxis and receptor internalization. Furthermore, differing from previously reported S1P1 antagonists, TASP0277308 demonstrated in vivo activities to induce lymphopenia, a block in T cell egress from the thymus, displacement of marginal zone B cells, and upregulation of CD69 expression on both T and B cells, all of which recapitulate phenotypes of S1P1-deficient lymphocytes. In a mouse collagen-induced arthritis model, TASP0277308 significantly suppressed the development of arthritis, even after the onset of disease. These findings provide the first chemical evidence to our knowledge that S1P1 antagonism is responsible for immunosuppression in the treatment of autoimmune diseases and also resolve the discrepancies between genetic and chemical studies on the functions of S1P1 in lymphocytes.

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“…1). The introduction of S1P after initial addition of IL-6 with TGF-β to cultures of CD4 T cells activated by TCR stimulation enhances differentiation of Th17 cells, but not Treg cells [20]. In this setting, S1P augmentation of terminal differentiation is a direct alternative to the enhancing effect of IL-23 or of IL-21 released by Th17 cells in an auto-enhancing mechanism.…”

Section: Complementary Actions Of Immune Cytokines and The S1p-s1p 1 mentioning

confidence: 96%

“…In some systems, the IL-21 secreted by Th17 cells provides positivefeedback stimulation of their development by serving as another alternative terminal differentiation factor. The introduction of IL-4 without and with IFN-γ in this culture model suppressed S1P-driven differentiation of Th17 cells as significantly as did addition of IL-27, another natural inhibitor of Th17 cell development [20].…”

Section: The S1p-s1p 1 Axis In Differentiation Of Adaptive Treg Cellsmentioning

confidence: 99%

“…The effects of the S1P-S1P 1 axis were observed later in differentiation than the effects of IL-4 and IL-6, and promoted terminal development of both adaptive Treg cells and Th17 effector cells as an alternative stimulus to other types of immune cytokines that also act as terminal differentiation factors. S1P is equal in activity to IL-23 as a terminal differentiation factor for WT Th17 effector T cells in an in vitro model where their development is initiated by TCR stimulation, TGF-β, IL-1, and IL-6 [20]. In some systems, the IL-21 secreted by Th17 cells provides positivefeedback stimulation of their development by serving as another alternative terminal differentiation factor.…”

Section: The S1p-s1p 1 Axis In Differentiation Of Adaptive Treg Cellsmentioning

confidence: 99%

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Regulation of the roles of sphingosine 1-phosphate and its type 1 G protein-coupled receptor in T cell immunity and autoimmunity

Goetzl

Liao

Huang

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The lipid mediator sphingosine 1-phosphate (S1P) and its type 1 G protein-coupled receptor (S1P 1 ) affect mammalian immunity through alterations in thymocyte emigration, differentiation of T cell subsets, lymphocyte trafficking in lymphoid organs and other tissues, T cell-dendritic cell and T cell-B cell interactions, and cytokine generation. Recent attention to effects of the S1P-S1P 1 axis on nonmigration functions of lymphocytes include delineation of a role in terminal differentiation and survival of Th17 effector cells and adaptive Treg cells of the CD4 T cell constellation, and a greater understanding of interactions of the S1P-S1P 1 axis with immune cytokines in lymphocyte survival and activities. This breadth of involvement of the S1P-S1P 1 axis in immune responses that often are altered in immunological diseases has provided many opportunities for novel therapeutic interventions. A spectrum of pharmacological and immunochemical agents is available that alter immunity by affecting either tissue and fluid concentrations of S1P or levels of expression and signaling activities of S1P 1 . Such agents have so far been beneficial in the settings of autoimmunity and rejection of transplanted organs, and are likely to become valuable constituents of combined drug programs.

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Cutting Edge: Alternative Signaling of Th17 Cell Development by Sphingosine 1-Phosphate

Cited by 111 publications

References 29 publications

Differential Production of IL-23 and IL-12 by Myeloid-Derived Dendritic Cells in Response to TLR Agonists

Differential Production of IL-23 and IL-12 by Myeloid-Derived Dendritic Cells in Response to TLR Agonists

Amelioration of Collagen-Induced Arthritis by a Novel S1P1 Antagonist with Immunomodulatory Activities

Regulation of the roles of sphingosine 1-phosphate and its type 1 G protein-coupled receptor in T cell immunity and autoimmunity

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