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

Slides:

Advertisements

Similar presentations

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

Advertisements

Multiple-checkpoint inhibition of thymic stromal lymphopoietin–induced TH2 response by TH17-related cytokines Sofia I. Bogiatzi, BSc, Maude Guillot-Delost,

Barbara Stanic, PhD, Willem van de Veen, PhD, Oliver F

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

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

Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu Amanda J. Reefer, MS, Kathryn.

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

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.

Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated.

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

IL-10 disrupts the Brd4-docking sites to inhibit LPS-induced CXCL8 and TNF-α expression in monocytes: Implications for chronic obstructive pulmonary disease

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,

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

Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival Jyoti Balhara, MSc, Lianyu Shan,

FOXP3+ CD4 T-cell maturity and responses to microbial stimulation alter with age and associate with early-life gut colonization Sophia Björkander, Maria.

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

Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human β-defensin-3 Kevin O. Kisich, PhD, Charles.

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

Eniko Sonkoly, MD, Anja Muller, MD, Antti I

Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin Mohan S. Maddur, DVM, Janakiraman Vani,

Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand Junyan Han, PhD, Azzeddine.

Selective and direct activation of human neutrophils but not eosinophils by Toll-like receptor 8 Markus Janke, PhD, Jens Poth, Vera Wimmenauer, Thomas.

Glucocorticoids promote intrinsic human TH17 differentiation

Flow cytometric measurement of STAT1 and STAT3 phosphorylation in CD4+ and CD8+ T cells—clinical applications in primary immunodeficiency diagnostics

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice László Hortobágyi, MS, Sonja Kierstein, PhD, Kateryna Krytska,

Dawn C. Newcomb, PhD, Madison G

CD19 controls Toll-like receptor 9 responses in human B cells

Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines Maryam Salimi,

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

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

Differential expression of functional chemokine receptors on human blood and lung group 2 innate lymphoid cells Cathryn A. Weston, PhD, Batika M.J. Rana,

Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin Sucai Liu, PhD,

Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen- presenting cells that induce proallergic T cells Susanne Ebner, PhD,

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

T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells Osamu Kaminuma, DVM, PhD, Fujiko Kitamura,

Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid Anne-Kathrin Kienzler, MSc, Marta Rizzi, MD,

Multiple-checkpoint inhibition of thymic stromal lymphopoietin–induced TH2 response by TH17-related cytokines Sofia I. Bogiatzi, BSc, Maude Guillot-Delost,

Targeting allergen to FcγRI reveals a novel TH2 regulatory pathway linked to thymic stromal lymphopoietin receptor Kathryn E. Hulse, PhD, Amanda J. Reefer,

Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis Shunya Mashiko, BPharm, Salim Bouguermouh, MD, PhD, Manuel.

Dichotomy of short and long thymic stromal lymphopoietin isoforms in inflammatory disorders of the bowel and skin Giulia Fornasa, PhD, Katerina Tsilingiri,

A thymic stromal lymphopoietin–responsive dendritic cell subset mediates allergic responses in the upper airway mucosa Guro R. Melum, MD, Lorant Farkas,

Impaired natural killer cell functions in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations Giovanna.

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,

Airway epithelial cells activate TH2 cytokine production in mast cells through IL-1 and thymic stromal lymphopoietin Deepti R. Nagarkar, PhD, Julie A.

Role of IL-35 in sublingual allergen immunotherapy

Mammalian target of rapamycin inhibition counterbalances the inflammatory status of immune cells in patients with chronic granulomatous disease Aurélie.

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

Human CD4+ T Lymphocytes with Remarkable Regulatory Functions on Dendritic Cells and Nickel-Specific Th1 Immune Responses Andrea Cavani, Francesca Nasorri,

Josée Lamoureux, PhD, Jana Stankova, PhD, Marek Rola-Pleszczynski, MD

Ganglioside GQ1b enhances Ig production by human PBMCs

Enhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity Iris Bellinghausen, PhD, Sebastian.

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

MicroRNA-4443 regulates mast cell activation by T cell–derived microvesicles Irit Shefler, PhD, Pazit Salamon, PhD, Francesca Levi-Schaffer, PharmD, Adam.

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

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

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

IgE induces transcriptional regulation of thymic stromal lymphopoietin in human airway smooth muscle cells Naresh Singh Redhu, MSc, Ali Saleh, PhD, Hai-Chon.

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,

Julie Negri, BA, S. Brandon Early, BA, John W

Thymic stromal lymphopoietin does not activate human basophils

Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells Junya Ohtake, PhD, Shun.

Intact IL-12 signaling is necessary for the generation of human natural killer cells with enhanced effector function after restimulation Venkateswara.

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

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

CARD9 mutations linked to subcutaneous phaeohyphomycosis and TH17 cell deficiencies Xiaowen Wang, MD, Wenyan Wang, PhD, Zhimiao Lin, MD, Xiaolin Wang,

Presentation transcript:

Thymic stromal lymphopoietin links keratinocytes and dendritic cell–derived IL-23 in patients with psoriasis Elisabetta Volpe, PhD, Lucia Pattarini, PhD, Carolina Martinez-Cingolani, PhD, Stephan Meller, MD, Marie-Helene Donnadieu, MSc, Sofia I. Bogiatzi, MD, PhD, Maria I. Fernandez, PhD, Maxime Touzot, MD, PhD, Jean-Christophe Bichet, MD, Fabien Reyal, MD, PhD, Maria Paola Paronetto, PhD, Andrea Chiricozzi, MD, Sergio Chimenti, MD, Francesca Nasorri, PhD, Andrea Cavani, MD, PhD, Andreas Kislat, MSc, Bernhard Homey, MD, PhD, Vassili Soumelis, MD, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 2, Pages 373-381.e4 (August 2014) DOI: 10.1016/j.jaci.2014.04.022 Copyright © 2014 Terms and Conditions

Fig 1 TSLP and TNF-α are epithelium-derived factors able to activate DCs and prime for IL-23 production by DCs. A-D, In blood DCs activated for 24 hours without (Fig 1, A and B) or with (Fig 1, C and D) CD40L, IL-23 was measured by means of ELISA (Fig 1, B and D), CD86 was analyzed by means of flow cytometry (Fig 1, A and C). E and F, IL-23 produced by skin DCs activated for 24 hours (Fig 1, E) or by blood DCs cocultured for 14 hours with anti-CD3/CD28–activated naive CD4 T cells was measured by means of ELISA (Fig 1, F). Results of 6 independent experiments are shown. MFI, Mean fluorescent intensity; ns, P > .05. *P < .05, **P < .005, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions

Fig 2 TSLP is expressed in human psoriatic skin. A and B, Frozen sections were stained with rat IgG isotype or 2 different anti-TSLP antibodies (3 representatives of 10 different donors; Fig 2, A) or with anti-TSLP in the absence or presence of 5 μg/mL recombinant human TSLP (1 representative of 3 different donors; Fig 2, B). C, Percentages of epidermal surface positively stained for TSLP across the entire section (average) and percentages of epidermal surface positively stained for TSLP (max) in the most positive field in healthy, AD, and psoriatic skin were compared. ns, P > .05. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions

Fig 3 CD40L is similarly expressed on lymphocytes from psoriatic and AD skin. A, Frozen sections were stained with anti-CD40L and anti-CD3 on psoriatic, AD, and normal skin (1 representative of 10 patients with psoriasis and 8 patients with AD). B, Counts of total positive cells for CD40L and CD3 in skin biopsy specimens from patients with psoriasis and patients with AD were compared. C and D, CD3 and CD40L expression were evaluated on psoriatic skin cells or PBMCs by using flow cytometry (Fig 3, C), and means ± SDs of 5 independent donors are reported (Fig 3, D). ns, P > .05. *P < .05. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions

Fig 4 IL-4 inhibits TSLP plus CD40L–mediated IL-23 production by DCs independently of STAT6. A-C, IL-23p19 and IL-12p40 expression (Fig 4, A), IL-23 production (Fig 4, B), and CD86 expression (Fig 4, C) by blood DCs cultured for 6 (Fig 4, A) or 24 (Fig 4, B and C) hours in different conditions were analyzed. D, IL-23 secretion by DCs cocultured for 14 hours with anti-CD3/CD28–activated naive CD4 T cells was measured by using ELISA. E, Inhibition of STAT6 expression in CD4 T cells and DCs by STAT6 inhibitor (1 μmol/L) was analyzed by using Western blotting. F, IL23p19, IL12p40, IL6, and CD86 transcripts were evaluated in DCs incubated for 6 hours and normalized to L34 gene expression (Fig 4, A and F). Means ± SDs of 4 independent experiments are reported (Fig 4, A-D and F). PSTAT, Phospho-STAT. ns, P > .05; *P < .05, **P < .005, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions

Fig E1 Naive CD4 T cells activated by anti-CD3/CD28 express high levels of CD40L. Expression of CD40L on resting naive CD4 T cells and after 6 hours of stimulation with anti-CD3/CD28 was analyzed by flow cytometry. One representative donor (A) and quantification of mean fluorescent intensity (MFI) for 7 donors (B) are shown. ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions

Fig E2 Goat isotype control staining. Frozen sections were stained with goat IgG isotype. Results are from 3 representatives of 10 different donors. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions

Fig E3 TSLP mRNA is overexpressed in lesional psoriatic skin. TSLP transcript was analyzed from skin biopsy specimens by means of real-time PCR, and values were normalized to GAPDH expression. *P < .05, **P < .005, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions

Fig E4 IL-23 inhibition by IL-4 in TSLP plus CD40L–primed DCs is dose dependent. Blood CD11c+ cells primed with TSLP or TSLP plus CD40L were stimulated with different doses of IL-4. IL23p19 and IL12p40 transcripts were measured by using real-time PCR, and values were normalized to L34 gene expression. Results are from 1 representative of 3 independent experiments. Journal of Allergy and Clinical Immunology 2014 134, 373-381.e4DOI: (10.1016/j.jaci.2014.04.022) Copyright © 2014 Terms and Conditions