Sphingosine 1‐phosphate induces Chemotaxis of immature dendritic cells and modulates cytokine‐release in mature human dendritic cells for emergence of Th2 immune responses

Idzko, Marco; Panther, Elisabeth; Corinti, Silvia; Morelli, Anna; Ferrari, Davide; Herouy, Yared; Dichmann, Stefan; Mockenhaupt, Maja; Gebicke‐Haerter, Peter J.; Virgilio, Francesco Di; Girolomoni, Giampiero; Norgauer, Johannes

doi:10.1096/fj.01-0625fje

Cited by 176 publications

(162 citation statements)

References 37 publications

(74 reference statements)

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…Similar results were obtained by collecting the supernatants of the co-cultures and detecting cytokine concentrations by ELISA, confirming the lower capacity of FT720-and FTY720-P-treated DC to promote Th1 differentiation and a shift towards Th2 cell differentiation as seen for S1P (Fig. 7B) [18].…”

Section: Resultssupporting

confidence: 82%

“…mRNA expression of S1P [1][2][3][4] has been reported for immature and mature human monocyte-derived DC [18]. Expression patterns of the S1P 1 , S1P 2 , S1P 3 , and Fig.…”

Section: Resultsmentioning

confidence: 87%

“…In human DC, S1P has been considered to inhibit their capacity to induce Th1 responses [18]. Thus, we wondered whether FTY720-or FTY720-Ptreated DC differ from control DC in their cytokine secretion profile.…”

Section: Resultsmentioning

confidence: 99%

“…Human dendritic cells (DC) express mRNA of the subtypes S1P 1 , S1P 2 , S1P 3 and S1P 4 [18]. S1P has been shown to affect both immature and mature DC by inducing chemotaxis in immature and modulating cytokine release in mature DC [18].…”

Section: Introductionmentioning

confidence: 99%

“…S1P has been shown to affect both immature and mature DC by inducing chemotaxis in immature and modulating cytokine release in mature DC [18].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The immunomodulator FTY720 interferes with effector functions of human monocyte‐derived dendritic cells

et al. 2005

View full text Add to dashboard Cite

The potent immunomodulator FTY720 elicits immunosuppression via acting on sphingosine 1-phosphate receptors (S1PR), thereby leading to an entrapment of lymphocytes in the secondary lymphoid tissue. To elucidate the potential in vitro effects of this drug on human monocyte-derived DC, we used low nanomolar therapeutic concentrations of FTY720 and phosphorylated FTY720 (FTY720-P) and investigated their influence on DC surface marker expression, protein levels of S1PR and DC effector functions: antigen uptake, chemotaxis, cytokine production, allostimulatory and Thpriming capacity. We report that both FTY720 and FTY720-P reduce chemotaxis of immature and mature DC. Mature DC generated in the presence of FTY720 or FTY720-P showed an impaired immunostimmulatory capacity and reduced IL-12 but increased IL-10 production. T cells cultured in the presence of FTY720-or FTY720-P-treated DC showed an altered cytokine production profile indicating a shift from Th1 toward Th2 differentiation. In treated immature and mature DC, expression levels for two S1PR proteins, S1P 1 and S1P 4, were reduced. We conclude that in vitro treatment with FTY720 affects DC features that are essential for serving their role as antigen-presenting cells. This might represent a new aspect of the overall immunosuppressive action of FTY720 and makes DC potential targets of further sphingolipid-derived drugs.

show abstract

Section: Resultssupporting

confidence: 82%

“…mRNA expression of S1P [1][2][3][4] has been reported for immature and mature human monocyte-derived DC [18]. Expression patterns of the S1P 1 , S1P 2 , S1P 3 , and Fig.…”

Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…S1P has been shown to affect both immature and mature DC by inducing chemotaxis in immature and modulating cytokine release in mature DC [18].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The immunomodulator FTY720 interferes with effector functions of human monocyte‐derived dendritic cells

et al. 2005

View full text Add to dashboard Cite

show abstract

Multiple Pathways to Control DC Migration

Otero¹,

Riboldi²,

Prete³

et al. 2006

Handbook of Dendritic Cells

View full text Add to dashboard Cite

Control of inflammatory diseases by pathogens: lipids and the immune system

Kleij

Yazdanbakhsh

2003

Eur J Immunol

View full text Add to dashboard Cite

Inflammatory diseases such as asthma and diabetes are rising in industrialized countries and the modern lifestyle that is associated with lower exposure to microbes has been held responsible for the increasing prevalence of these diseases. Several studies have shown an inverse association between pathogen-exposure and allergy or autoimmunity. The mechanisms behind such protective effects have been investigated at the epidemiological, cellular and molecular level and have provided data on the ability of lipids either derived directly from pathogens or up-regulated as a result of an infection to down-regulate immune responses and thereby control inflammatory diseases. In this mini-review, recent findings and new concepts relating to the immunosuppressive effects of endogenous lipids and those encountered upon exposure to bacteria, protozoa and particularly helminths are discussed. The overview focuses on the modulation of interactions between the antigen-presenting compartment and T cells to start an anti-inflammatory "program" with potential to regulate disease processes. PGJ 2 Lyso-PA: Lysophosphatidic acid Lyso-PC: Lysophosphatidylcholine Lyso-PS: Lysophosphatidylserine LXA4: Lipoxin A4 TLR2: Toll-like receptor 2 Treg cell: Regulatory T cell The inverse relationship between infections and allergiesThe prevalence of allergies has increased significantly over the last few decades, particularly in industrialized countries. Within these countries, a negative association has been found between certain childhood infections and allergic diseases [1,2]. Lifestyles such as anthroposophy or traditional farming -thought to be associated with higher exposure to pathogens or pathogen-derived products -have been shown to be protective against atopic disorders [3,4]. Furthermore, in low-income countries, where exposure to pathogens is higher, the prevalence of allergy is often lower than in industrialized countries [5]. Studies examining the relationship between allergies and parasitic infections in areas where transmission is intense have revealed that children with chronic helminth infections have a lower risk of wheeze or of skin-prick-test positivity for house-dust mite [6,7].The question of how infections can prevent allergies has received much attention in the last few years. Although many bacteria and viruses induce Th1 responses, which in turn may prevent the development of Th2 responses, helminths -which are potent Th2 inducers -are surprisingly also protective [7]. This has led to the question of what additional mechanisms, acting downstream of the induction/initiation phase, suppress allergic inflammation. Such mechanisms downstream of T cell polarization would work to protect not only from Th2 inflammation but also from Th1 inflammation, and their absence would explain the concurrent rise at the population level in allergies (Th2 diseases) and autoimmunities (often Th1 diseases) [8]. The possibility that immunosuppressive regulatory responses stimulated during repeated/intense exposure to pathogens or pathogenderi...

show abstract

Sphingosine 1‐phosphate induces Chemotaxis of immature dendritic cells and modulates cytokine‐release in mature human dendritic cells for emergence of Th2 immune responses

Cited by 176 publications

References 37 publications

The immunomodulator FTY720 interferes with effector functions of human monocyte‐derived dendritic cells

The immunomodulator FTY720 interferes with effector functions of human monocyte‐derived dendritic cells

Multiple Pathways to Control DC Migration

Control of inflammatory diseases by pathogens: lipids and the immune system

Contact Info

Product

Resources

About