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Indoleamine 2,3-dioxygenase–dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model  Yousef.

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Presentation on theme: "Indoleamine 2,3-dioxygenase–dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model  Yousef."— Presentation transcript:

1 Indoleamine 2,3-dioxygenase–dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model  Yousef A. Taher, MSc, Benoit J.A. Piavaux, MSc, Reneé Gras, BSc, Betty C.A.M. van Esch, BSc, Gerard A. Hofman, BSc, Nanne Bloksma, PhD, Paul A.J. Henricks, PhD, Antoon J.M. van Oosterhout, PhD  Journal of Allergy and Clinical Immunology  Volume 121, Issue 4, Pages e2 (April 2008) DOI: /j.jaci Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Outline of the immunotherapy protocol in a murine model of asthma and the immunotherapy intervention studies. A, OVA-sensitized mice received 1 mg or 100 μg of OVA immunotherapy subcutaneously (s.c.) and were challenged with OVA aerosols. B, Daily intervention with the IDO inhibitor 1MT or PBS during immunotherapy (B1) or during challenge (B2) or daily intervention with tryptophan (TRP), kynurenine (KYN), KA, 3-OH-KYN, 3-OH-AA, QUINA, XA, or saline (B3-B5). Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Effects of IDO inhibition on the efficacy of immunotherapy (IT). A, Airway responsiveness 1 day after OVA aerosol challenge. B, Eosinophil numbers in the BALF. C, Eosinophil numbers in lung tissue. D, IL-5 and IL-13 levels in the BALF. Values are expressed as means ± SEMs (n = 7-8). ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001 compared with sham/PBS-treated mice. #P < .05, ##P < .01, and ###P < .001 compared with 1 mg of OVA immunotherapy/PBS–treated mice. $$P < .01 compared with PBS-challenged mice. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Effects of tryptophan (TRP) or its metabolite, kynurenine (KYN), on the efficacy of optimal or suboptimal immunotherapy (IT). A, Eosinophil numbers and IL-5 levels. B, IL-13 and IL-10 levels in the BALF. Values are expressed as means ± SEMs (n = 6). ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001 compared with sham/saline-treated mice. #P < .05 and ##P < .01 compared with 100 μg of OVA immunotherapy/saline–treated mice. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Effects of kynurenines on the efficacy of suboptimal immunotherapy (IT). A, Eosinophil numbers and IL-5 levels. B, IL-13 and IL-10 levels in the BALF 1 day after airway challenge with OVA aerosols. Values are expressed as means ± SEMs (n = 6). ∗P < .05 and ∗∗P < .01 compared with sham/saline-treated mice. #P < .05 and P < .01 compared with 100 μg of OVA immunotherapy/saline–treated mice. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Effects of 3-OH-KYN and XA alone or in combination on the efficacy of suboptimal immunotherapy (IT) on eosinophil numbers in the BALF. Values are expressed as means ± SEMs (n = 6). ∗∗P < .01 compared with sham/saline-treated mice. #P < .05 compared with 100 μg of OVA immunotherapy/saline–treated mice. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Effect of tryptophan (TRP) administration on the efficacy of suboptimal OVA immunotherapy (100 μg) on eosinophil numbers in the BALF 1 day after OVA aerosol challenge. Values are expressed as means ± SEMs (n = 6). ∗P < .05 compared with sham-treated mice. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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