TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

Slides:

Advertisements

Similar presentations

Maria B. Sukkar, PhD, Shaoping Xie, PhD, Nadia M

Advertisements

Triggering of specific Toll-like receptors and proinflammatory cytokines breaks allergen- specific T-cell tolerance in human tonsils and peripheral blood

Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2 Natalija Novak, MD, Nihal Mete, MD, Caroline.

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Mechanisms of IFN-γ–induced apoptosis of human skin keratinocytes in patients with atopic dermatitis Ana Rebane, PhD, Maya Zimmermann, PhD, Alar Aab,

Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong Th17/Th1 T-cell responses Anja Hänsel,

Russell S. Traister, MD, PhD, Crystal E. Uvalle, BS, Gregory A

Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema Sabine Zeller, MSc, Claudio Rhyner, PhD, Norbert Meyer, MD, Peter.

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response Miriam Wittmann, MD, Mareike Alter, Tanja.

Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic.

Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use Daniel A. Searing, MD, Yong Zhang, PhD, James.

Toll-like receptor 7–induced naive human B-cell differentiation and immunoglobulin production Mark C. Glaum, MD, PhD, Shilpi Narula, MD, Decheng Song,

Dual nature of T cell–epithelium interaction in chronic rhinosinusitis

IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis Norbert Meyer, MD, Maya Zimmermann, PhD,

Histamine H2 receptor stimulation upregulates TH2 chemokine CCL17 production in human M2a macrophages Susanne Mommert, PhD, Karl Gregor, MD, Kristine.

Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4 inhibitor treatment Lennart M. Roesner, PhD, Petra Kienlin, Gabriele.

FcεRI-mediated amphiregulin production by human mast cells increases mucin gene expression in epithelial cells Shigeru Okumura, DDS, PhD, Hironori Sagara,

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Infliximab induces downregulation of the IL-12/IL-23 axis in 6-sulfo-LacNac (slan)+ dendritic cells and macrophages Patrick M. Brunner, MD, Frieder Koszik,

Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis Hari Balaji, MSc, Annice Heratizadeh,

Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic.

Evidence of a role for B cell–activating factor of the TNF family in the pathogenesis of chronic rhinosinusitis with nasal polyps Atsushi Kato, PhD,

Human mast cells arise from a common circulating progenitor

Dawn C. Newcomb, PhD, Madison G

Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use Daniel A. Searing, MD, Yong Zhang, PhD, James.

Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation

Staphylococcus aureus enhances the tight junction barrier integrity in healthy nasal tissue, but not in nasal polyps Can Altunbulakli, MSc, Rita Costa,

Anionic surfactants and commercial detergents decrease tight junction barrier integrity in human keratinocytes Mu Xian, MD, PhD, Paulina Wawrzyniak,

Toll-like receptor 9 suppression in plasmacytoid dendritic cells after IgE-dependent activation is mediated by autocrine TNF-α John T. Schroeder, PhD,

The innate antiviral response upregulates IL-13 receptor α2 in bronchial fibroblasts Gemma Campbell-Harding, PhD, Hannah Sawkins, BSc, Nicole Bedke, PhD,

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps Sarah Peterson, MD, Julie A. Poposki, MS, Deepti.

Transmembrane activator and CAML interactor (TACI) haploinsufficiency results in B- cell dysfunction in patients with Smith-Magenis syndrome Javier Chinen,

Miriam Wittmann, MD, Jana Zeitvogel, Dong Wang, MD, Thomas Werfel, MD

Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J

Katherine G. MacDonald, BSc, Nicholas A. J

David M. Pyle, BS, Victoria S. Yang, MD, Rebecca S

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

Inhibition of ABCC4 potentiates combination beta agonist and glucocorticoid responses in human airway epithelial cells Ryan D. Huff, MSc, Christopher.

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma Fei Huang, PhD, Shinichiro Wachi, PhD,

Inhibition of angiogenesis by IL-32: Possible role in asthma

Activin A is an acute allergen-responsive cytokine and provides a link to TGF-β– mediated airway remodeling in asthma Christian Karagiannidis, MD, Gabriele.

Vitamin D Analog Calcipotriol Suppresses the Th17 Cytokine–Induced Proinflammatory S100 “Alarmins” Psoriasin (S100A7) and Koebnerisin (S100A15) in Psoriasis

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis Wen Hao Wu, PhD,

IL-17 in atopic eczema: Linking allergen-specific adaptive and microbial-triggered innate immune response Kilian Eyerich, MD, Davide Pennino, PhD, Claudia.

Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis Deepti R. Nagarkar, PhD, Julie A. Poposki,

Streptococcus pyogenes–induced cutaneous lymphocyte antigen–positive T cell– dependent epidermal cell activation triggers TH17 responses in patients with.

Receptor-interacting protein kinase 3 controls keratinocyte activation in a necroptosis- independent manner and promotes psoriatic dermatitis in mice

The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells Juha Punnonen, MD, PhD, Hans Yssel, PhD,

Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis Margarete Niebuhr, MD, Helena Scharonow, MS, Merle Gathmann,

Increased activation-induced cell death of high IFN-γ–producing TH1 cells as a mechanism of TH2 predominance in atopic diseases Tunc Akkoc, PhD, Pieter.

IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts Séverine Létuvé, PhD, Stéphane Lajoie-Kadoch, MSc, Séverine Audusseau,

Amplification of Toll-like receptor–mediated signaling through spleen tyrosine kinase in human B-cell activation Shigeru Iwata, MD, PhD, Kunihiro Yamaoka,

Anionic surfactants and commercial detergents decrease tight junction barrier integrity in human keratinocytes Mu Xian, MD, PhD, Paulina Wawrzyniak,

Harald Renz, MD, Chaya Brodie, PhD, Katherine Bradley, BS, Donald Y. M

Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis Axel Trautmann, MDa, Mübeccel Akdis, MDa, Peter.

Staphylococcus aureus α-toxin modulates skin host response to viral infection Lianghua Bin, PhD, Byung Eui Kim, MD, Anne Brauweiler, PhD, Elena Goleva,

T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma Axel Trautmann, MDa, Peter Schmid-Grendelmeier, MDa,

Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-γ and IL-4 Michael B. Soyka, MD, Paulina Wawrzyniak,

Jenny Seltmann, PhD, Lennart M

Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis Eva Gros, MSc, Caroline Bussmann,

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Regulation of IL-13 receptor α1 expression and signaling on human tonsillar B- lymphocyte subsets Oumnia Hajoui, PhD, Huaien Zheng, MD, PhD, Julie Guay,

Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects Hiroyuki Fujita, MD, PhD, Maciej Chalubinski, MD, PhD,

IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses Willem van de Veen, MSc, Barbara.

IL-31 is associated with cutaneous lymphocyte antigen–positive skin homing T cells in patients with atopic dermatitis Janine Bilsborough, PhD, Donald.

Transforming growth factor β1 increases fibronectin deposition through integrin receptor α5β1 on human airway smooth muscle Lyn M. Moir, PhD, Janette.

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Thymic stromal lymphopoietin links keratinocytes and dendritic cell–derived IL-23 in patients with psoriasis Elisabetta Volpe, PhD, Lucia Pattarini,

Presentation transcript:

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert Meyer, MD, Tomasz Basinski, PhD, Flurina Meiler, PhD, Burgler Simone, PhD, Stefan Woehrl, MD, Katharina Moritz, MD, Thomas Eiwegger, MD, Peter Schmid-Grendelmeier, MD, Lajos Kemeny, MD, Cezmi A. Akdis, MD Journal of Allergy and Clinical Immunology Volume 127, Issue 1, Pages 200-207.e10 (January 2011) DOI: 10.1016/j.jaci.2010.11.005 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 The TNF-α and TWEAK combination induces keratinocyte (KC) apoptosis. Keratinocytes were stimulated with 10 ng/mL TNF-α and 100 ng/mL TWEAK. A and B, Kinetic cell death of 2 independent experiments (mean ± SD) in primary healthy (Fig 1, A) and transformed (Fig 1, B) keratinocytes. C and D, Annexin V and 7-AAD staining of healthy, AD, and psoriatic keratinocytes 4 days after stimulation with cytokines (n = 5 for each group). Fig 1, D, indicates 1 representative experiment (mean ± SD). Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 The TNF-α and TWEAK combination induces apoptosis in artificial skin equivalents. Artificial skin equivalents were cultured with 10 ng/mL TNF-α and 100 ng/mL TWEAK for 5 days. Positive cells were detected by means of TUNEL. One representative example is shown of 2 independent experiments. DAPI, 4′,6-Diamidino-2-phenylindole; u.s., unstimulated. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Fn14 and TNFR1 are expressed on keratinocytes and not regulated by TNF-α and TWEAK, as shown by means of quantitative real-time PCR (A; data shown represent means ± SDs, n = 3 for each group), flow cytometric analysis (B), and immunohistochemistry (C). Fig 3, B and C, show 1 representative example of healthy keratinocytes of 3 independent experiments. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 TNF-α and TWEAK–induced cell death takes place through TNFR1 and Fn14. Keratinocytes (KC) were stimulated with 10 ng/mL TNF-α and 100 ng/mL TWEAK. A, Anti-TNFR1 mAb, but not anti-TNFR2 mAb, blocked TNF-α and TWEAK–induced keratinocyte death. B, Induction of keratinocyte death in combination with TNF-α by anti-Fn14 mAb (ITEM-1 and ITEM-2). Fig 4, A and B, show data representing means ± SDs of 2 independent experiments. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 TWEAK upregulates TNF-α mRNA in healthy, AD, and psoriatic keratinocytes (A). TWEAK does not enhance TNF-α–induced TNF-α mRNA expression (F). Keratinocytes were stimulated with 100 ng/mL TWEAK (A, D, and E), 100 ng/mL TRAIL (B), 500 ng/mL mAb anti-Fas (C), and 10 ng/mL TNF-α (E and F). Means ± SDs of 3 independent experiments are shown. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Fn14 is highly expressed in healthy, AD, and psoriatic skin, whereas TWEAK is highly expressed in the epidermis of AD skin but not in psoriatic and normal skin. Immunohistochemistry (IHC) and immunofluorescent (IF) staining in healthy (A), AD (B), and psoriatic (C) skin are depicted with the appropriate isotype control (i.c.). One representative example is shown (n = 3 for each group). DAPI, 4′,6-Diamidino-2-phenylindole. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

The combination of TNF-α with TRAIL or anti-Fas mAb and the combination of TWEAK and TRAIL does not enhance keratinocyte (KC) apoptosis compared with stimulation with these molecules alone in healthy, AD, and psoriatic keratinocytes. Keratinocytes were stimulated with 10 ng/mL TNF-α, 100 ng/mL TWEAK, 100 ng/mL TRAIL, and 500 ng/mL anti-Fas mAb. Data shown represent means ± SDs (n = 5 for each group). Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fn14, TNFR1, and TNFR2 mRNA are not regulated by TNF-α and TWEAK Fn14, TNFR1, and TNFR2 mRNA are not regulated by TNF-α and TWEAK. Keratinocytes were stimulated with 10 ng/mL TNF-α and 100 ng/mL TWEAK. There were no differences among healthy donors, donors with AD, and donors with psoriasis (n = 3 for each group). Data shown represent means ± SDs of healthy keratinocytes. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

The simultaneous presence of TNF-α and TWEAK in cell culture induces efficient keratinocyte (KC) death. Primary keratinocytes were stimulated with 10 ng/mL TNF-α and 100 ng/mL TWEAK in the presence of 10 ng/mL cycloheximide for 48 hours. A, The mean ± SD of 3 independent experiments is shown. B, Data of 1 representative experiment are shown. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Addition of recombinant human (rh) TWEAK to anti-TWEAK mAb significantly decreased TWEAK-positive staining to undetectable levels. TWEAK immunofluorescence staining in AD lesional skin was performed with and without adding 5 μg/mL rhTWEAK to anti-TWEAK mAb. One representative example is shown (n = 2). DAPI, 4′,6-Diamidino-2-phenylindole. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

A, TNF-α, TWEAK, TNFR1, TNFR2, and Fn14 mRNA expression in healthy control, AD, and psoriatic lesional skin biopsy specimens. Data shown represent means ± SDs (n = 5 for healthy, n = 8 for AD, and n = 6 for psoriatic skin biopsy specimens). B, TNF-α is upregulated in AD and psoriatic lesional skin compared with that seen in healthy control skin. Immunofluorescent (IF) staining in AD lesional, healthy control, and psoriatic lesional skin are depicted with the appropriate isotype control (i.c.). One representative example is shown (n = 2 for each group). DAPI, 4′,6-Diamidino-2-phenylindole. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Serum levels of TWEAK did not show any differences among healthy subject, patients with AD, and patients with psoriasis. TWEAK serum levels were measured by means of ELISA. Blood of patients with AD and patients with psoriasis was taken during an acute exacerbation of disease. Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

TWEAK expression in keratinocytes TWEAK expression in keratinocytes. A, Basal TWEAK mRNA expression in unstimulated healthy, AD, and psoriatic keratinocytes compared with basal TNF-α mRNA expression (mean ± SD, n = 3). B, TWEAK mRNA regulation in healthy, AD, and psoriatic keratinocytes (72 hours' stimulation, mean ± SD, n = 3). C-E, TWEAK (mean ± SD, n = 2), TNF-α, and TRAIL mRNA regulation (24 hours' stimulation). F, TWEAK expression in keratinocyte supernatants (mean ± SD, n = 2). Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

TWEAK mRNA basal expression in resting T cells does not show any differences among TH1, TH2, Treg, and TH17 cells. Data shown represent means ± SDs (n = 3 for each group). Journal of Allergy and Clinical Immunology 2011 127, 200-207.e10DOI: (10.1016/j.jaci.2010.11.005) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions