Does reduced zona pellucida binding protein 2 (ZPBP2) expression on chromosome 17q21 protect against asthma? Marina Miller, MD, PhD, Christine Vuong,

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Presentation transcript:

Does reduced zona pellucida binding protein 2 (ZPBP2) expression on chromosome 17q21 protect against asthma? Marina Miller, MD, PhD, Christine Vuong, BS, Meghan Farrell Garcia, MD, Peter Rosenthal, BS, Sudipta Das, PhD, Ning Weng, PhD, Alexa Pham, PhD, Yu Jin Kim, BS, David H. Broide, MB, ChB Journal of Allergy and Clinical Immunology Volume 142, Issue 2, Pages 706-709.e4 (August 2018) DOI: 10.1016/j.jaci.2018.04.011 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 ZPBP2 expression in lung and lung cells. A, Six chromosome 17q21–localized genes (IKZF3, ZPBP2, GSDMB, ORMDL3, LRRC3C, and GSDMA) are depicted, with arrows indicating the direction of transcription. B, WT mice were challenged with HDM intranasally on days 0, 7, 14, and 21. On day 24, lung tissues (WT no HDM and WT HDM; n = 8 mice per group) were processed for quantitation of Zpbp2 mRNA copy number values. C, Zpbp2 mRNA copy number values were quantitated in mouse testes and purified populations of mouse eosinophils (Eos; bone marrow), T cells (spleen), B cells (spleen), macrophages (Mac; bone marrow), smooth muscle cells (SMC; (trachea), fibroblasts (Fibr; lung), and the epithelial cell line MLE12 (Epi), as well as lungs of a Zpbp2 KO mouse (ZPBP2 KO). D, Zpbp2 mRNA copy number values were quantitated in mouse airway epithelial cells obtained by using bronchial brushing and FACS-sorted lung eosinophils, T cells, and macrophages before and after HDM challenge of WT mice (n = 3 mice per group). E-G, Lung thymic stromal lymphopoietin (TSLP; Fig 1, E), lung IL-13 (Fig 1, F), and lung IFN-γ (Fig 1, G) levels were quantitated by using ELISA (n = 8 mice per group). NS, Not significant. Journal of Allergy and Clinical Immunology 2018 142, 706-709.e4DOI: (10.1016/j.jaci.2018.04.011) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Reduced AHR and inflammation in HDM-challenged Zpbp2 KO mice. A and B, WT or Zpbp2 KO mice (Fig 2, A, male group; Fig 2, B, female group) were challenged with HDM intranasally on days 0, 7, 14, and 21. On day 24, airway resistance in response to methacholine was measured by using flexiVent. WT plus HDM versus WT without HDM: **P < .01 (methacholine, 48 mg/mL); Zpbp2 KO plus HDM versus Zpbp2 KO without HDM: P = not significant (methacholine, 48 mg/mL). C-F, Lung tissue from WT or Zpbp2 KO mice (Fig 2, C and E, male groups; Fig 2, D and F, female groups) was processed for immunohistochemistry to detect MBP+ eosinophils (Fig 2, C and D) and CD4+ lymphocytes (Fig 2, E and F). G and H, Sera from WT or Zpbp2 KO mice (Fig 2, G, male group; Fig 2, H, female group) was processed for ELISA to detect IgE. NS, Not significant. Journal of Allergy and Clinical Immunology 2018 142, 706-709.e4DOI: (10.1016/j.jaci.2018.04.011) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Zpbp2-deficient versus WT mice: BAL fluid eosinophils and T cells. Zpbp2-deficient or WT mice (n = 8 mice per group) were challenged with HDM intranasally on days 0, 7, 14, and 21. On day 24, BAL fluid eosinophil counts and levels of T-cell inflammation were quantitated. Numbers of Wright-Giemsa–stained BAL fluid eosinophils (A and B) and BAL fluid lymphocytes (C and D) were quantitated by using light microscopy. *P < .05 and ***P <.001. NS, Not significant. Journal of Allergy and Clinical Immunology 2018 142, 706-709.e4DOI: (10.1016/j.jaci.2018.04.011) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 ORMDL3 mRNA levels in Zpbp2-deficient versus WT mice. Levels of ORMDL3 mRNA, as well as ORMDL1 and ORMDL2 mRNA, were quantitated by using qPCR in the lungs of Zpbp2-deficient and WT mice (n = 8 mice per group). NS, Not significant. Journal of Allergy and Clinical Immunology 2018 142, 706-709.e4DOI: (10.1016/j.jaci.2018.04.011) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions