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Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells  Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel,

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Presentation on theme: "Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells  Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel,"— Presentation transcript:

1 Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells 
Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel, MD, Matthias Wenghoefer, MD, Bernd Niederhagen, MD, Thomas Bieber, MD, PhD, Stefaan Bergé, MD, Natalija Novak, MD  Journal of Allergy and Clinical Immunology  Volume 121, Issue 2, Pages e1 (February 2008) DOI: /j.jaci Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 oLCs express TLR4. A, TLR4 transcripts were detected by RT-PCR in full oral mucosa tissue as well as (B) in highly enriched CD1a+ oLCs. C, oLCs were analyzed for their CD14 (plot, y-axis) and Langerin/CD207 (plot, x-axis) expression. All CD1a+ cells expressed LC-specific marker Langerin/CD207 (representative plot of n = 3). Next to a CD14neg/CD207high (blue oval) population, a CD14low/CD207high (green oval) and a CD14high/CD207high (red oval) population was detected with highest TLR4 expression on CD14high/CD207high (red line, upper histogram; n = 3). Black lines represent respective isotype controls. Values represent percentage of gated cells positive for investigated marker. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 TLR4 ligation on oLCs increases expression of tolerogenic surface molecules. Freshly isolated oLCs (upper panel) express high amounts of B7-H2 (blue lines; second column) and B7-H3 (blue lines; third column), whereas B7-H1 was virtually absent (blue lines; first column). TLR4 ligation (lower panel) led to upregulation of B7-H1 (blue lines; first column) and B7-H3 (blue lines; third column) on oLCs (red lines, respective isotype control) compared with unstimulated oLCs (middle panel). Representative histograms of n = 5. Values represent rFI. ∗Significant to 0h; #significant to control/CTR. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Differential costimulatory molecule expression on TLR4 ligation on oLCs. Representative histograms of CD80 (first column, blue line) and CD86 (second column, blue line) are shown. Red lines represent respective isotype controls. Compared with freshly isolated oLCs (upper panel), unstimulated oLCs (control, middle panel) and TLR4 ligation on oLCs led to upregulation of CD80 (first column, blue line) and CD86 (blue lines; second column; n = 5). Values represent rFI. ∗Significant to 0h; #significant to control/CTR. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 TLR4 ligation on oLCs increases their anti-inflammatory properties. A, Ligation of TLR4 led to an increase of IL-10 production by oLCs (blue bars) in comparison with oLCs that were left unstimulated (gray bars; n = 10). B, TLR4 ligation of oLCs (+oLC/+TLR4 ligation) reduced their stimulatory capacity toward T cells compared with T cells cocultured with unstimulated oLCs (T/oLC); n = 5. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 oLCs preactivated by TLR4 induce T cells with tolerogenic properties. Compared with T cells alone (T) and T cells cocultured with unstimulated oLC (+oLC), T cells cocultured with TLR4-activated oLC s(+oLC+TLR4-ligation) showed increased production of IL-10 (A) and TGF-β1 (B), n = 5. C, T cells were gated by CD4+ and CD25high and further analyzed by Foxp3 expression (n = 6; representative dot plots and histograms). Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 TLR4 ligation on oLCs induces preferentially TH1 T cells. Cytokine production in supernatants of T cells cultured alone (upper panel, red plots), with unstimulated oLCs (second upper panel, blue plots), or TLR4 preactivated oLCs (third upper panel, green plots) was detected by beads in different near infrared channels (y-axis). Detected fluorescence (x-axis) correlated with cytokine concentrations. Histograms, lower panel, red graph = T cells alone; blue graph = T cells cultured with unstimulated oLCs; green graph = T cells cultured with TLR4 activated oLCs; n = 5, values in plots represent cytokine concentrations ± SEMs. ∗Significant to T cells alone; #significant to oLCs without TLR ligation. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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