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Interferon-α-conditioned human monocytes combine a Th1-orienting attitude with the induction of autologous Th17 responses: role of IL-23 and IL-12.

Santini SM, Lapenta C, Donati S, Spadaro F, Belardelli F, Ferrantini M - PLoS ONE (2011)

Bottom Line: Priming of naïve CD4 T cells with autologous IFN-DC in the presence of either SEA or anti-CD3, resulted, in addition to a prominent expansion of CXCR3+ IFN-γ-producing CD4 Th1 cells, in the emergence of two distinct subsets of IL-17-producing CD4 T cells: i) a predominant Th17 population selectively producing IL-17 and expressing CCR6; ii) a minor Th1/Th17 population, producing both IL-17 and IFN-γ.After phagocytosis of apoptotic cells, IFN-DC induced Th17 cell expansion and IL-17 release.Notably, the use of neutralizing antibodies revealed that IL-23 was an essential cytokine in mediating Th17 cell development by IFN-DC.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.

ABSTRACT
IFN-α exerts multiple effects leading to immune protection against pathogens and cancer as well to autoimmune reactions by acting on monocytes and dendritic cells. We analyzed the versatility of human monocytes conditioned by IFN-α towards dendritic cell differentiation (IFN-DC) in shaping the autologous T-helper response. Priming of naïve CD4 T cells with autologous IFN-DC in the presence of either SEA or anti-CD3, resulted, in addition to a prominent expansion of CXCR3+ IFN-γ-producing CD4 Th1 cells, in the emergence of two distinct subsets of IL-17-producing CD4 T cells: i) a predominant Th17 population selectively producing IL-17 and expressing CCR6; ii) a minor Th1/Th17 population, producing both IL-17 and IFN-γ. After phagocytosis of apoptotic cells, IFN-DC induced Th17 cell expansion and IL-17 release. Notably, the use of neutralizing antibodies revealed that IL-23 was an essential cytokine in mediating Th17 cell development by IFN-DC. The demonstration of the IFN-DC-induced expansion of both Th1 and Th17 cell populations reveals the intrinsic plasticity of these DC in orienting the immune response and provides a mechanistic link between IFN-α and the onset of autoimmune phenomena, which have been correlated with both IL-17 production and exposure to IFN-α.

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Related in: MedlinePlus

Estimation of the emergence of Th17 cells by analysis of surrogate cell marker expression.Dot plot analysis of the expression of CCR6 and CCR4 on CD4 T cells after a 6-day stimulation with SEA or anti-CD3 coated beads in the presence of autologous DC. The results of one representative experiment out of five independently performed are shown. In all cases, the analysis was performed on electronically gated CD4+ T cells.
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pone-0017364-g004: Estimation of the emergence of Th17 cells by analysis of surrogate cell marker expression.Dot plot analysis of the expression of CCR6 and CCR4 on CD4 T cells after a 6-day stimulation with SEA or anti-CD3 coated beads in the presence of autologous DC. The results of one representative experiment out of five independently performed are shown. In all cases, the analysis was performed on electronically gated CD4+ T cells.

Mentions: In the light of the cytokine milieu produced by IFN-DC, we evaluated whether these APC could favor the emergence of Th17 CD4 lymphocytes. In this set of experiments, anti-CD3-coated beads were used to stimulate the naïve CD4 T cells in the co-cultures with autologous DC, to obtain a higher percentage of responding CD4 T cells and amplify the phenomenon. Remarkably, the FACS analysis demonstrated the concomitant expression of CCR4 and CCR6 (Fig. 4), that is assumed to identify the Th17 CD4 subset [12], [13], on a fraction of CD4 T cells primed in the presence of autologous IFN-DC.


Interferon-α-conditioned human monocytes combine a Th1-orienting attitude with the induction of autologous Th17 responses: role of IL-23 and IL-12.

Santini SM, Lapenta C, Donati S, Spadaro F, Belardelli F, Ferrantini M - PLoS ONE (2011)

Estimation of the emergence of Th17 cells by analysis of surrogate cell marker expression.Dot plot analysis of the expression of CCR6 and CCR4 on CD4 T cells after a 6-day stimulation with SEA or anti-CD3 coated beads in the presence of autologous DC. The results of one representative experiment out of five independently performed are shown. In all cases, the analysis was performed on electronically gated CD4+ T cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046151&req=5

pone-0017364-g004: Estimation of the emergence of Th17 cells by analysis of surrogate cell marker expression.Dot plot analysis of the expression of CCR6 and CCR4 on CD4 T cells after a 6-day stimulation with SEA or anti-CD3 coated beads in the presence of autologous DC. The results of one representative experiment out of five independently performed are shown. In all cases, the analysis was performed on electronically gated CD4+ T cells.
Mentions: In the light of the cytokine milieu produced by IFN-DC, we evaluated whether these APC could favor the emergence of Th17 CD4 lymphocytes. In this set of experiments, anti-CD3-coated beads were used to stimulate the naïve CD4 T cells in the co-cultures with autologous DC, to obtain a higher percentage of responding CD4 T cells and amplify the phenomenon. Remarkably, the FACS analysis demonstrated the concomitant expression of CCR4 and CCR6 (Fig. 4), that is assumed to identify the Th17 CD4 subset [12], [13], on a fraction of CD4 T cells primed in the presence of autologous IFN-DC.

Bottom Line: Priming of naïve CD4 T cells with autologous IFN-DC in the presence of either SEA or anti-CD3, resulted, in addition to a prominent expansion of CXCR3+ IFN-γ-producing CD4 Th1 cells, in the emergence of two distinct subsets of IL-17-producing CD4 T cells: i) a predominant Th17 population selectively producing IL-17 and expressing CCR6; ii) a minor Th1/Th17 population, producing both IL-17 and IFN-γ.After phagocytosis of apoptotic cells, IFN-DC induced Th17 cell expansion and IL-17 release.Notably, the use of neutralizing antibodies revealed that IL-23 was an essential cytokine in mediating Th17 cell development by IFN-DC.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.

ABSTRACT
IFN-α exerts multiple effects leading to immune protection against pathogens and cancer as well to autoimmune reactions by acting on monocytes and dendritic cells. We analyzed the versatility of human monocytes conditioned by IFN-α towards dendritic cell differentiation (IFN-DC) in shaping the autologous T-helper response. Priming of naïve CD4 T cells with autologous IFN-DC in the presence of either SEA or anti-CD3, resulted, in addition to a prominent expansion of CXCR3+ IFN-γ-producing CD4 Th1 cells, in the emergence of two distinct subsets of IL-17-producing CD4 T cells: i) a predominant Th17 population selectively producing IL-17 and expressing CCR6; ii) a minor Th1/Th17 population, producing both IL-17 and IFN-γ. After phagocytosis of apoptotic cells, IFN-DC induced Th17 cell expansion and IL-17 release. Notably, the use of neutralizing antibodies revealed that IL-23 was an essential cytokine in mediating Th17 cell development by IFN-DC. The demonstration of the IFN-DC-induced expansion of both Th1 and Th17 cell populations reveals the intrinsic plasticity of these DC in orienting the immune response and provides a mechanistic link between IFN-α and the onset of autoimmune phenomena, which have been correlated with both IL-17 production and exposure to IFN-α.

Show MeSH
Related in: MedlinePlus