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Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin–basophil axis  Mario Noti,

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Presentation on theme: "Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin–basophil axis  Mario Noti,"— Presentation transcript:

1 Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin–basophil axis  Mario Noti, PhD, Brian S. Kim, MD, Mark C. Siracusa, PhD, Gregory D. Rak, VMD, PhD, Masato Kubo, PhD, Amin E. Moghaddam, MD, Quentin A. Sattentau, PhD, Michael R. Comeau, BSc, Jonathan M. Spergel, MD, PhD, David Artis, PhD  Journal of Allergy and Clinical Immunology  Volume 133, Issue 5, Pages e6 (May 2014) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Epicutaneous sensitization promotes antigen-induced food allergy. A, Experimental protocol. B, TSLP protein in the skin. C, Allergy score. D, OVA-specific serum IgE levels. E, Hematoxylin and eosin staining from the jejunum. Scale bar = 100 μm. Arrows, Tissue-infiltrating granulocytes. F, Type 2 cytokine expression in the jejunum. G, Frequencies of mast cells in the lamina propria. H, Jejunal mouse mast cell protease 1 (Mcpt1) and Mcpt2 expression. Results are from 3 to 4 mice per group. Data are representative of 3 independent experiments. i.g., Intragastric; ND, no disease. *P ≤ .05; **P ≤ .01; and ***P ≤ .001. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 TSLP–TSLP receptor responses mediate antigen-induced food allergy. A, Experimental protocol. B, Allergy score. C, OVA-specific serum IgE levels. D, Hematoxylin and eosin staining from the jejunum. Scale bar = 100 μm. Arrows, Tissue-infiltrating granulocytes. E, Type 2 cytokine expression in the jejunum. F, Frequencies of mast cells in the lamina propria. G, Jejunal mouse mast cell protease 1 (Mcpt1) and Mcpt2 expression. Results are from 3 to 4 mice per group. Data are representative of 3 independent experiments. i.g., Intragastric; ND, no disease; ns, not significant. *P ≤ .05; **P ≤ .01; and ***P ≤ .001. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 TSLP is sufficient to promote antigen-induced intestinal food allergy. A, Experimental protocol. B, Allergy score. C, OVA-specific serum IgE levels. D, Hematoxylin and eosin staining from the jejunum. Scale bar = 100 μm. Arrows, Tissue-infiltrating granulocytes. E, Type 2 cytokine expression in the jejunum. F, Frequencies of mast cells in the lamina propria. G, Jejunal mouse mast cell protease (Mcpt1) and Mcpt2 expression. Results are from 3 mice per group. Data are representative of 3 independent experiments. i.d., Intradermal; i.g., intragastric; ND, no disease. *P ≤ .05 and **P ≤ .01. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 AD-like skin lesions are associated with accumulation of TSLP-elicited basophils in the skin. A, Experimental protocol. B, Frequencies of basophils in the skin. C, Hematoxylin and eosin staining from the skin. Scale bar = 100 μm. D, Ear thickness measurement. E, TH2 cytokine responses in antigen-restimulated skin-draining lymph nodes. Results are from 3 to 4 mice per group. Data are representative of 3 independent experiments. nd, Not detected. **P ≤ .01 and ***P ≤ .001. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 TSLP-elicited basophil responses regulate antigen-induced food allergy. A, Experimental protocol. B, Allergy score. C, OVA-specific serum IgE levels. D, Hematoxylin and eosin staining from the jejunum. Scale bar = 100 μm. Arrows, Tissue-infiltrating granulocytes. E, Type 2 cytokine expression in the jejunum. F, Frequencies of mast cells in the lamina propria. G, Jejunal mouse mast cell protease 1 (Mcpt1) and Mcpt2 expression. Results are from 3 to 5 mice per group. Data are representative of 3 independent experiments. i.g., Intragastric; ND, no disease; nd, not detected. *P ≤ .05; **P ≤ .01; and ***P ≤ .001. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 TSLP-elicited basophils are sufficient to promote intestinal food allergy. A, Experimental protocol. B, Allergy score. C, OVA-specific serum IgE levels. D, Hematoxylin and eosin staining from the jejunum. Scale bar = 100 μm. Arrows, Tissue-infiltrating granulocytes. E, Type 2 cytokine expression in the jejunum. F, Frequencies of mast cells in the lamina propria. G, Jejunal mouse mast cell protease 1 (Mcpt1) and Mcpt2 expression. Results are from 3 mice per group. Data are representative of 3 independent experiments. i.g., Intragastric; ND, no disease. *P ≤ .05; **P ≤ .01; and ***P ≤ .001. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E1 Clinical allergy score. Allergy scores from WT BALB/c mice epicutaneously sensitized with OVA and orally challenged with OVA or BSA as a control are shown. Results are from 3 mice per group. Data are representative of 2 individual experiments. ND, No disease. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E2 Epicutaneous sensitization with CPE. A, Experimental protocol. B, Allergy score. C, CPE-specific serum IgE levels. D, Hematoxylin and eosin staining from the jejunum. Scale bar = 50 μm. Arrows, Tissue-infiltrating granulocytes. E, Jejunal type 2 cytokine expression levels. F, Frequencies of small intestinal lamina propria mast cells. Results are from 3 to 4 mice per group. Data are representative of 2 independent experiments. i.g., Intragastric; ND, no disease; ns, not significant. *P ≤ .05 and **P ≤ .01. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Fig E3 Epicutaneous sensitization on tape-stripped skin promotes intestinal food allergy. A, Experimental protocol. B, Allergy score. C, OVA-specific serum IgE levels. D, Frequencies of small intestinal lamina propria mast cells. Results are from 3 to 4 mice per group. Data are representative of 2 independent experiments. ND, No disease. *P ≤ .05. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Fig E4 Antigen-induced intestinal food allergy is dependent on IgE. A, Allergy score. B, OVA-specific serum IgE levels. Results are from 3 mice per group. Data are representative of 2 or more independent experiments. ND, No disease; nd, not detected. **P ≤ .01. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Fig E5 TSLP-dependent basophil frequencies in the skin. For statistical analysis, MC903 plus OVA Tslpr+/+ or MC903 plus OVA Tslpr−/− mice are compared. Results are from 3 mice per group. Data are representative of 2 independent experiments. **P ≤ .01. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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