James J. Lee, PhD, Cheryl A. Protheroe, BA, Huijun Luo, PhD, Sergei I

Slides:

Advertisements

Similar presentations

Frank Siebenhaar, MD, Markus Magerl, MD, Eva M. J

Advertisements

Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4–mediated suppression of IL-10 Susanne Kaesler, PhD, Thomas Volz, MD, Yuliya.

Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Striking deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis Jens U. Ponikau, MD, David A. Sherris,

Platelets play important roles in the late phase of the immediate hypersensitivity reaction Risa Tamagawa-Mineoka, MD, PhD, Norito Katoh, MD, PhD, Saburo.

Eosinophils and itch: Partners in crime or strange bedfellows?

Ryan H. Dougherty, MD, Sukhvinder S

Intravenous immunoglobulin treatment abrogates transplacental autoantibody transfer in a murine pemphigus model Sachiko Ono, MD, PhD, Gyohei Egawa, MD,

Human versus mouse eosinophils: “That which we call an eosinophil, by any other name would stain as red” James J. Lee, PhD, Elizabeth A. Jacobsen, PhD,

Allergy prevention starts before conception: Maternofetal transfer of tolerance protects against the development of asthma Tobias Polte, PhD, Christian.

Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in mice Hiroichi Nagai, PhD, Toru Abe, PhD, Itaru Yamaguchi, PhD, Kanako.

Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation

Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis Paul J. Bryce, PhD, Rustom Falahati, PhD,

Dexamethasone induces ω3-derived immunoresolvents driving resolution of allergic airway inflammation Katerina Pyrillou, PhD, Aikaterini-Dimitra Chairakaki,

Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis Lisa M. Bartnikas, MD, Michael F. Gurish,

Autocrine hemokinin-1 functions as an endogenous adjuvant for IgE-mediated mast cell inflammatory responses Tina L. Sumpter, PhD, Chin H. Ho, MD, Anna.

Type I IL-1 Receptor Mediates IL-1 and Intracellular IL-1 Receptor Antagonist Effects in Skin Inflammation Gaby Palmer, Dominique Talabot-Ayer, Gürkan.

Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation Si-Yen Liu, PhD, Wei-Zhi Wang,

Β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses Zhonghua Zhang, MD, Jocelyn.

A Novel Histologic Scoring System to Evaluate Mucosal Biopsies From Patients With Eosinophilic Esophagitis Cheryl Protheroe, Samantha A. Woodruff, Giovanni.

Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

Color-coded real-time cellular imaging of lung T-lymphocyte accumulation and focus formation in a mouse asthma model Akihiro Hasegawa, PhD, Katsuhiro.

Signaling through FcRγ-associated receptors on dendritic cells drives IL-33–dependent TH2-type responses Melissa Y. Tjota, BA, Cara L. Hrusch, PhD, Kelly.

Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A.

Liver X Receptor Activators Display Anti-Inflammatory Activity in Irritant and Allergic Contact Dermatitis Models: Liver-X-Receptor-Specific Inhibition.

CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling Jennifer Kearley, PhD, Douglas S. Robinson,

Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma Muhannad Hassan, MD, Taisuke Jo, MD, PhD, Paul-André Risse, PhD,

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

Silvana Balzar, MD, Matthew Strand, PhD, Diane Rhodes, PhD, Sally E

Cheng-Chiu Huang, PhD, Yu Shin Kim, PhD, William P

James J. Lee, PhD, Cheryl A. Protheroe, BA, Huijun Luo, PhD, Sergei I

Beatrix Schäfer, PhD, Adrian M

Eosinophilic esophagitis: Epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment Amir F. Kagalwalla, MD,

Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1–high T cells Jong Hoon.

Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis Chisa Nakashima, MD, Atsushi Otsuka, MD, PhD, Akihiko.

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

Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype Nicolas Gaudenzio, PhD, Camille Laurent, MD, Salvatore Valitutti,

Renee Rawson, BS, Tom Yang, BS, Robert O

Frank Siebenhaar, MD, Markus Magerl, MD, Eva M. J

Humanized anti–IFN-γ (HuZAF) in the treatment of psoriasis

Mast cell–derived plasminogen activator inhibitor type 1 promotes airway inflammation and remodeling in a murine model of asthma Ara Jo, PhD, Sun H.

Peanut-induced intestinal allergy is mediated through a mast cell–IgE–FcεRI–IL-13 pathway Meiqin Wang, MD, PhD, Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

Sabine Leisten, MSc, Michiko K

Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma Muhannad Hassan, MD, Taisuke Jo, MD, PhD, Paul-André Risse, PhD,

The Differential Role of L-Selectin and ICAM-1 in Th1-Type and Th2-Type Contact Hypersensitivity Asako Ogawa, Ayumi Yoshizaki, Koichi Yanaba, Fumihide.

The cardiomyocyte protein αT-catenin contributes to asthma through regulating pulmonary vein inflammation Stephen Sai Folmsbee, G.R. Scott Budinger,

Sarita Sehra, PhD, Weiguo Yao, PhD, Evelyn T. Nguyen, MS, Nicole L

Allergic skin sensitization promotes eosinophilic esophagitis through the IL-33–basophil axis in mice Nicholas Venturelli, BS, Willem S. Lexmond, MD,

Liver X Receptor Activators Display Anti-Inflammatory Activity in Irritant and Allergic Contact Dermatitis Models: Liver-X-Receptor-Specific Inhibition.

Src homology 2 domain–containing inositol 5-phosphatase 1 deficiency leads to a spontaneous allergic inflammation in the murine lung Sun-Young Oh, PhD,

Oral administration of a synthetic agonist of Toll-like receptor 9 potently modulates peanut-induced allergy in mice Fu-Gang Zhu, PhD, Ekambar R. Kandimalla,

Kirthana Ganeshan, BS, Colleen V

The EGFR Is Required for Proper Innervation to the Skin

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment

Activation of human mast cells through the platelet-activating factor receptor Naoki Kajiwara, PhD, Tomomi Sasaki, BSc, Peter Bradding, DM, Glenn Cruse,

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Duy Pham, PhD, Sarita Sehra, PhD, Xin Sun, PhD, Mark H. Kaplan, PhD

An Important Role of Lymphatic Vessels in the Control of UVB-Induced Edema Formation and Inflammation Kentaro Kajiya, Michael Detmar Journal of Investigative.

Prostaglandin E receptor subtype EP3 in conjunctival epithelium regulates late-phase reaction of experimental allergic conjunctivitis Mayumi Ueta, MD,

No defect in T-cell priming, secondary response, or tolerance induction in response to inhaled antigens in Fms-like tyrosine kinase 3 ligand–deficient.

Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4–mediated suppression of IL-10 Susanne Kaesler, PhD, Thomas Volz, MD, Yuliya.

The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced intestinal anaphylaxis Meiqin Wang, MD, PhD, Julita Ramirez, DVM, PhD,

Esophageal eosinophilia caused by milk proteins: From suspicion to evidence based on 2 case reports Soledad Terrados Cepeda, MD, Dario Antolin-Amerigo,

MicroRNA-155 is essential for TH2-mediated allergen-induced eosinophilic inflammation in the lung Carina Malmhäll, BSc, Sahar Alawieh, BSc, You Lu, PhD,

Anti-IgE efficacy in murine asthma models is dependent on the method of allergen sensitization Daniel B. Tumas, DVM, PhDa, Betty Chan, BSb, Winifred.

Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation Takumi Kiwamoto,

Therapeutic efficacy of an anti–IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma Felix R. Shardonofsky, MD,

The extra domain A of fibronectin is essential for allergen-induced airway fibrosis and hyperresponsiveness in mice Martin Kohan, MSc, Andres F. Muro,

Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation Takumi Kiwamoto,

Presentation transcript:

Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice James J. Lee, PhD, Cheryl A. Protheroe, BA, Huijun Luo, PhD, Sergei I. Ochkur, PhD, Gregory D. Scott, BS, Katie R. Zellner, MS, Randall J. Raish, MS, Mark V. Dahl, MD, Miriam L. Vega, MD, MPH, Olivia Conley, Rachel M. Condjella, PhD, Jake A. Kloeber, Joseph L. Neely, Yash S. Patel, Patty Maizer, MS, Andrew Mazzolini, MA, Allison D. Fryer, PhD, Noah W. Jacoby, David B. Jacoby, MD, Nancy A. Lee, PhD Journal of Allergy and Clinical Immunology Volume 135, Issue 2, Pages 477-487.e1 (February 2015) DOI: 10.1016/j.jaci.2014.07.003 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Toxicant contact exposure protocols to either DNFB or TMA. Experimental and control mice were sensitized by exposure to DNFB (A) or TMA (B) and subsequently toxicant-challenged (left ear) in the time frames described, with the contralateral right ear of each mouse challenged using vehicle alone (DNFB, olive oil:acetone [3:1] or TMA, olive oil:acetone [4:1]) to provide negative controls for exposure. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 The toxicant-contact skin reactions that follow exposure to TMA, but not DNFB, elicit a robust differential recruitment and/or accumulation of eosinophils. Infiltrating eosinophils in ear biopsies following exposure to TMA or DNFB were identified by immunohistochemistry using a rat anti-mouse major basic protein monoclonal antibody; negative control biopsies were derived from contralateral ears exposed to vehicle alone (DNFB, olive oil:acetone [3:1] or TMA, olive oil:acetone [4:1]). Scale bar = 100 μm. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Ear tissue biopsies demonstrate that eosinophil-mediated activities contribute to TMA-induced inflammatory and remodeling responses. A, Hematoxylin-eosin stained sections of ear tissue biopsies from wild-type and eosinophil-deficient PHIL mice exposed to TMA (negative controls are contralateral ears exposed to vehicle alone (olive oil:acetone [4:1]). Scale bar = 50 μm. B, Representative picrosirius-red-stained ear sections from wild-type and age-matched (12 weeks postpartum) eosinophil-deficient PHIL mice (visualized under polarized light). E, Epidermis; M, muscularis; CA, cartilage. Scale bar = 100 μm. C, Under polarized light, the sub-epidermal interstitial area within each entire ear biopsy from 5 to 9 mice per group was evaluated at a magnification of 200×, evaluating the area underlying ≥0.7 mm linear length of epidermis. The extent and intensity of picrosirius red staining was quantified as the sum total (∑) of pixel values (pixel number × average pixel intensity within the region surrounding the basement membrane of epidermis normalized to the total linear length of epidermis evaluated). n.s., Not significant, *P < .05. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 The remodeling events linked with eosinophils infiltrating the skin contribute to the increased ear thickness that occurs following exposure to TMA. Ear thickness (mm) of previously sensitized wild type (clear circle) vs eosinophil-deficient PHIL (black circle) mice challenged with TMA was measured on protocol day 15 using a micrometer as a surrogate maker for tissue edema; contralateral ears exposed to vehicle alone (olive oil:acetone [4:1]) were used as negative controls. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 TMA-induced skin inflammatory responses lead not only to eosinophil accumulation but also to eosinophil degranulation and the release of secondary granule components within the interstitium underlying the epidermis. EPX-mAb-based immunohistochemistry of ear biopsies (n = 5/cohort) demonstrated that a spectrum of eosinophil infiltration and degranulation levels occur in TMA-challenged wild-type mice. A, Representative moderate (160×, 1.8 mm2 field-of-view) power photomicrographs were used to identify the maximum foci of eosinophil infiltration in each biopsy (Table I). Scale bar = 100μm. B, Representative photomicrographs (400× hpf [0.29 mm2 field-of-view]) of each level of degranulation (Table I) as determined by EPX-mAb-based immunohistochemistry (magenta staining cells and extracellular matrix regions). Scale bar = 100 μm. C, The EAI algorithm, representing both eosinophil tissue infiltration and eosinophil degranulation (Table I), was used to quantify eosinophil-mediated activities in the skin of TMA-challenged wild-type vs PHIL mice; negative controls are vehicle-alone treated ears (olive oil:acetone [4:1]). *P < .05. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 TMA-induced inflammation elicits an eosinophil-dependent increase of sensory nerve innervation of the skin. A, Representative confocal immunofluorescence images of wild-type and eosinophil-deficient PHIL mice following challenge with TMA. Control exposures were vehicle-alone (acetone:olive oil [4:1], identifying all dermal [PGP 9.5; green]) and sensory dermal (substance P [red]) nerves. Scale bar = 100 μm. B, The quantification of the TMA-mediated increase in substance P-expressing nerve density (relative to vehicle-alone treated contralateral ears) demonstrated that unlike total innervation, which did not change between wild-type and PHIL ears treated with vehicle-alone (acetone:olive oil [4:1]), the density of substance P-expressing nerves increased (relative to contralateral ear treated with vehicle alone) in TMA-treated wild-type ears (n = 4), with ears from TMA-treated eosinophil-deficient PHIL mice displaying no increase in these nerves (n = 3). *P < .05. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 The induced itching occurring in response to TMA-mediated inflammation is an eosinophil-dependent phenomenon. TMA-mediated itching events were assessed from time-lapsed videography following the last TMA exposure (ie, the night between protocol days 14 and 15). Quantification of itching events in wild-type (clear circle) vs eosinophil-deficient PHIL (black circle) mice was assessed relative to the contralateral control ear from the same mouse by 3 intra/inter-observer blinded investigators (n = 7-8 mice/group). These data showed that the induced itching associated with TMA-mediated inflammation was significantly lower in the absence of eosinophils (PHIL) compared with itching events occurring in wild-type mice. *P < .05. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 The toxicant-contact skin reactions occurring in eosinophil-deficient PHIL mice (relative to wild type) following exposure to TMA are accompanied by lower numbers of resident mast cells and variable levels of mast cell degranulation. Infiltrating mast cells and the extent of mast cell degranulation in ear biopsies following exposure to TMA were assessed by immunohistochemistry using an anti-mast cell tryptase monoclonal antibody; negative control biopsies were derived from contralateral ears exposed to vehicle alone (olive oil:acetone [4:1]). These data showed that TMA-treated wild-type mice uniformly displayed significant inflammatory changes that included increases in mast cell numbers and extensive degranulation. In contrast, TMA-treatment of PHIL mice elicited only nominal increases in mast cell numbers while inducing variable levels of mast cell degranulation. Scale bar = 1 mm. Journal of Allergy and Clinical Immunology 2015 135, 477-487.e1DOI: (10.1016/j.jaci.2014.07.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions