Differential roles for the IL-9/IL-9 receptor α-chain pathway in systemic and oral antigen–induced anaphylaxis Heather Osterfeld, BSc, Richard Ahrens,

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Presentation transcript:

Differential roles for the IL-9/IL-9 receptor α-chain pathway in systemic and oral antigen–induced anaphylaxis Heather Osterfeld, BSc, Richard Ahrens, BSc, Richard Strait, MD, Fred D. Finkelman, MD, Jean-Christophe Renauld, PhD, Simon P. Hogan, PhD Journal of Allergy and Clinical Immunology Volume 125, Issue 2, Pages 469-476.e2 (February 2010) DOI: 10.1016/j.jaci.2009.09.054 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Critical role for the IL-9/IL-9R pathway in anaphylaxis induced by oral antigen challenge. A, Diarrhea occurrence in vehicle (Veh)– or OVA-sensitized intragastric (i.g.) OVA-challenged WT, Il9R−/−, and Il9−/− mice. A and B, Serum mouse mcpt-1 levels (Fig 1, B) and temperature change (Fig 1, C) from 0 to 60 minutes after the sixth intragastric vehicle or OVA challenge in OVA-sensitized WT, Il9R−/−, and Il9−/− mice. Data in Fig 1, A, are represented as a percentage of diarrhea occurrence after a number of OVA challenges. The fraction indicates the number of mice with diarrhea out of the total number of mice in that group. Data in Fig 1, B and C, are representative after the sixth intragastric vehicle or OVA challenge in OVA-sensitized WT, Il9R−/−, and Il9−/− mice. Fig 1, B, Four to 8 mice per group from n = 3 experiments. ∗P < .05. Fig 1, C, Individual symbols represent 1 mouse. ∗P < .001. Journal of Allergy and Clinical Immunology 2010 125, 469-476.e2DOI: (10.1016/j.jaci.2009.09.054) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 No role for the IL-9/IL-9R pathway in anti-IgE–mediated passive systemic anaphylaxis. A, Rectal temperature in control immunoglobulin (Ig)– and anti-IgE–treated WT, Il9−/−, and Il9R−/− mice. Total IgE levels (B) and mast cells per high-power field (HPF) in the tongue (C), ear skin (D), and small bowel (E) in control Ig– and anti-IgE–treated WT, Il9−/− and Il9R−/− mice. F, Serum mcpt-1 concentrations in control Ig and anti-IgE mAb–challenged WT, Il9−/−, and Il9R−/− mice. Fig 2, A and F, n = 3 to 7 mice per group. ∗P < .05 compared with WT control Ig–treated mice. Fig 2, C through E, n = 4 mice per group. Fig 2, B, n = 4-6 mice per group from duplicate experiments. n.s., Not significant. OD; optical density. Journal of Allergy and Clinical Immunology 2010 125, 469-476.e2DOI: (10.1016/j.jaci.2009.09.054) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 No role for the IL-9/IL-9R pathway in anti-FcγRII/III–mediated passive systemic anaphylaxis. A and B, Total IgG1 and IgG2a levels in WT, Il9−/−, and Il9R−/− mice. C, Rectal temperature response of WT, Il9−/−, and Il9R−/− mice to intravenous injection of anti-FcγRII/III mAb or control immunoglobulin (control Ig; J1.2). Fig 3, A and B, n = 4 mice per group from duplicate experiments. Fig 3, C, n = 5-11 mice per group. ∗P < .05 compared with WT control mice. Journal of Allergy and Clinical Immunology 2010 125, 469-476.e2DOI: (10.1016/j.jaci.2009.09.054) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 No role for the IL-9/IL-9R pathway in parenteral antigen–induced anaphylaxis. Rectal temperatures (A) and serum mcpt-1 concentrations (B) in OVA-sensitized WT, Il9−/−, and Il9R−/− mice injected intravenously with OVA or vehicle (Veh). Fig 4, A and B, n = 4 mice per group from duplicate experiments. ∗P < .05 compared with WT control. Journal of Allergy and Clinical Immunology 2010 125, 469-476.e2DOI: (10.1016/j.jaci.2009.09.054) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 No role for the IL-9/IL-9R pathway in IgE- or IgG-mediated parenteral OVA-induced systemic anaphylaxis. Rectal maximum temperature changes and serum mcpt-1 concentrations in OVA-sensitized mice desensitized with immunoglobulin control (control Ig; GL117 + J1.2), anti-IgE mAb, or anti-FcγRII/III mAb and challenged intravenously with OVA are shown. A, WT mice. B, Il9−/− mice. C, Il9R−/− mice. Data represent means ± SEMs; n = 3–6 mice per group from duplicate experiments. ∗P < .05 compared with control Ig. Journal of Allergy and Clinical Immunology 2010 125, 469-476.e2DOI: (10.1016/j.jaci.2009.09.054) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Critical role for the IL-9/IL-9R pathway in anaphylaxis induced by oral antigen challenge. Mean number of mast cells per high-power field (hpf) in the intestine (A) and serum OVA-specific IgE levels (B) in saline- or OVA-sensitized OVA-challenged WT, Il9R−/−, and Il9−/− mice. Fig E1, A and B, Four to 8 mice per group from n = 3 experiments. ∗P < .05. Veh, Vehicle. Journal of Allergy and Clinical Immunology 2010 125, 469-476.e2DOI: (10.1016/j.jaci.2009.09.054) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions