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IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells  Claire Galand, PhD, Juan Manuel Leyva-Castillo, PhD, Juhan.

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Presentation on theme: "IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells  Claire Galand, PhD, Juan Manuel Leyva-Castillo, PhD, Juhan."— Presentation transcript:

1 IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells 
Claire Galand, PhD, Juan Manuel Leyva-Castillo, PhD, Juhan Yoon, PhD, Alex Han, BA, Margaret S. Lee, MD, PhD, Andrew N.J. McKenzie, PhD, Michael Stassen, PhD, Michiko K. Oyoshi, PhD, Fred D. Finkelman, MD, Raif S. Geha, MD  Journal of Allergy and Clinical Immunology  Volume 138, Issue 5, Pages (November 2016) DOI: /j.jaci Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Journal of Allergy and Clinical Immunology 2016 138, 1356-1366DOI: (10
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 1 Il33 expression in skin is upregulated by mechanical injury and allergic skin inflammation. A, Il33 mRNA levels in unmanipulated (unm.) skin and skin obtained 6 hours after tape stripping (T/S) from WT BALB/c mice (n = 3). B, IL33 mRNA levels in unmanipulated (unm.) skin and skin obtained 6 hours after scratching from 2 healthy nonallergic adults. C, IL-33 levels in supernatants of an area of 1 cm2 of unmanipulated (unm.) or tape-stripped mouse skin after culture for 1 hour (n = 6 per group). D, IL-33 levels in serum obtained from unmanipulated (unm.) mouse skin and 1, 6, and 24 hours after tape stripping (n = 6 per group). Columns and vertical bars in Fig 1, A-C, represent means and SEMs, respectively. Symbols and vertical bars in Fig 1, D, represent means and SEMs. ns, Not significant. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 2 ST2 deficiency reduces food-induced anaphylaxis in epicutaneously sensitized mice. A and B, Experimental design protocol for oral anaphylaxis in epicutaneously sensitized mice (Fig 2, A, upper panel), change in body temperature (Fig 2, A, lower panel), and serum mMCP-1 levels (Fig 2, B) in epicutaneously sensitized mice. EC sens, Epicutaneous sensitization; Sal, saline. C, Total jejunal MC numbers (left panel) and MMC9 numbers (right panel) in unsensitized mice versus mice epicutaneously sensitized with OVA (n = 4 each group). D and E, Serum OVA-specific IgE (Fig 2, D) and IL-4 and IL-13 secretion by splenocytes (Fig 2, E) in mice epicutaneously sensitized with saline (S) or OVA (O; n = 4-5 each group). F and G, Change in body temperature (Fig 2, F) and serum mMCP-1 levels (Fig 2, G) in WT mice passively sensitized with anti-TNP IgE mAb and orally challenged with TNP-BSA. mMCP-1 levels were measured 60 minutes after challenge. Each experiment has been repeated at least a second time independently with similar number of mice and similar results. Symbols and vertical bars in Fig 2, A and F, represent means and SEMs. Columns and vertical bars in Fig 2, B-E and G, represent means and SEMs. ns, Not significant. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 3 ST2 blockade reduces food-induced anaphylaxis in epicutaneously sensitized mice. A and B, Change in body temperature (Fig 3, A) and serum mMCP-1 (Fig 3, B) levels after oral OVA challenge of epicutaneously sensitized WT mice treated 48 and 24 hours before oral challenge with rat anti-ST2 mAb DJ8 (αST2) or rat IgG1 isotype control (Ctrl.). C and D, Change in body temperature (Fig 3, C) and serum mMCP-1 levels (Fig 3, D) in WT mice epicutaneously sensitized with OVA, previously orally challenged with OVA, rested for 2 weeks, and then administered anti-ST2 DJ8 mAb or isotype control mAb (Ctrl.) on −2 and day −1 and then rechallenged orally with OVA. mMCP-1 levels were measured 60 minutes after challenge. Each experiment is a pool of 2 independent experiments. Symbols and vertical bars in Fig 3, A and C, represent means and SDs. Columns and vertical bars in Fig 3, B and D, represent means and SDs. EC sens, Epicutaneous sensitization; Sal, saline. *P < .05 and ***P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 4 ST2 expression by MCs is important for food-induced anaphylaxis in epicutaneously sensitized mice. A, Change in body temperature after oral OVA challenge of epicutaneously sensitized WT or KitW-sh/W-sh BALB/c mice. B, Serum OVA-specific IgE levels in epicutaneously sensitized mice. C, Experimental design protocol for oral anaphylaxis in epicutaneously sensitized BMMC-reconstituted KitW-sh/W-sh BALB/c mice. i.p., Intraperitoneal; SCF, stem cell factor. D, Representative fluorescence-activated cell sorting staining (left panel) and quantitation (right panel) of CD45+Lin−c-Kit+FcεRI+ cells in the peritoneal lavage of WT, KitW-sh/W-sh BALB/c, and KitW-sh/W-sh BALB/c mice reconstituted with WT or ST2-deficient BMMCs (n = 4-5 per group). E, Jejunal MC numbers (left panel) and representative chloroacetate esterase staining of MCs in the jejunum (right panel, ×400 magnification; n = 4-5 per group). F, Change in body temperature after oral OVA challenge of OVA-sensitized KitW-sh/W-sh BALB/c mice reconstituted with WT or ST2-deficient BMMCs or left unreconstituted. Each experiment has been repeated at least a second time independently with similar numbers of mice and similar results. Symbols and vertical bars in Fig 4, A and F, represent means and SEMs. Columns and vertical bars in Fig 4, B, D, and E represent means and SEMs. EC sens, EC sensitization; Sal, saline. ns, Not significant. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 5 IL-33 signaling in BMMCs promotes antigen-driven IgE-mediated degranulation. A-D, Representative fluorescence-activated cell sorting contour plots of surface LAMP-1 staining in gated WT IgE+ cells (Fig 5, A), percentages of WT (Fig 5, B) and ST2-deficient (Fig 5, D) LAMP-1+ cells, and mean fluorescence intensity of sLAMP1 expression on WT cells (Fig 5, C) in BMMCs cultured overnight with anti-DNP IgE and the indicated stimuli and then challenged with medium or DNP-HSA, as shown. Each experiment has been repeated at least a second time independently with 3 to 5 BMMC cultures per group. Columns and vertical bars represent means and SEMs. Ctrl., Control; ns, not significant. *P < .05 and ***P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 6 IL-33 and FcεRI crosslinking synergize in driving TH2 cytokine mRNA expression by MCs. A-C, mRNA levels of Il6 (Fig 6, A), Il13 (Fig 6, B), and Il9 (Fig 6, C) in WT BMMCs cultured overnight with anti-DNP IgE and the indicated stimuli and then challenged with medium or DNP-HSA as shown and analyzed 1 hour after challenge (n = 6 BMMC cultures per group). Each experiment has been repeated a second time independently with similar number of samples and similar results. Columns and vertical bars represent means and SEMs. ns, Not significant. ***P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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