Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells Luzheng Xue, PhD,

Slides:

Advertisements

Similar presentations

Human group 2 innate lymphoid cells do not express the IL-5 receptor

Advertisements

Activation of mast cells by double-stranded RNA: evidence for activation through Toll- like receptor 3 Marianna Kulka, PhD, Lena Alexopoulou, PhD, Richard.

Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial Eve Hornsby, PhD, Paul E. Pfeffer,

Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production Laura Maggi, PhD, Gianni Montaini, BSc, Alessio Mazzoni,

Mechanical injury polarizes skin dendritic cells to elicit a TH2 response by inducing cutaneous thymic stromal lymphopoietin expression Michiko K. Oyoshi,

Vitamin D enhances production of soluble ST2, inhibiting the action of IL-33 Paul E. Pfeffer, MRCP, Yin-Huai Chen, MSc, Grzegorz Woszczek, PhD, Nick C.

Characterization of a novel human mast cell line that responds to stem cell factor and expresses functional FcεRI Tanya M. Laidlaw, MD, John W. Steinke,

Liping Xie, MD, John T. Schroeder, PhD, Jacqueline M

Epigenetic regulation of established human type 1 versus type 2 cytokine responses Ruey-Chyi Su, PhD, Allan B. Becker, MD, Anita L. Kozyrskyj, PhD, Kent.

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation Regina K. Rowe, MD, PhD, David M. Pyle, MD,

Prostaglandin E2 inhibits mast cell–dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor Jesper Säfholm,

Production of chemokines and proinflammatory and antiinflammatory cytokines by human alveolar macrophages activated by IgE receptors Philippe Gosset,

Ramses Ilarraza, PhD, Yingqi Wu, Christopher D

IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin Robert J. Salmond, PhD, Ananda S. Mirchandani,

Neonatal rhinovirus induces mucous metaplasia and airways hyperresponsiveness through IL-25 and type 2 innate lymphoid cells Jun Young Hong, MS, J. Kelley.

D prostanoid receptor 2 (chemoattractant receptor–homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects.

Differential control of TH1 versus TH2 cell responses by the combination of low-dose steroids with β2-adrenergic agonists Elena Goleva, PhD, Annegret.

Efficient cytokine-induced IL-13 production by mast cells requires both IL-33 and IL-3 Ilkka S. Junttila, MD, PhD, Cynthia Watson, BSc, Laura Kummola,

The histamine-cytokine network in allergic inflammation

Dawn C. Newcomb, PhD, Madison G

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

Functional analysis of protective IL1RL1 variants associated with asthma risk Vladimir Ramirez-Carrozzi, PhD, Amy Dressen, MS, Patrick Lupardus, PhD,

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

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,

Frank Kirstein, PhD, Natalie E

Jovana Maric, MSc, Avinash Ravindran, MSc, Luca Mazzurana, MSc, Åsa K

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

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,

Katherine G. MacDonald, BSc, Nicholas A. J

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

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,

Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia Steven.

Human TH2 cells respond to cysteinyl leukotrienes through selective expression of cysteinyl leukotriene receptor 1 Celine N. Parmentier, MSc, Elisabeth.

Fibronectin is a TH1-specific molecule in human subjects

Zoulfia Allakhverdi, PhD, Michael R. Comeau, BSc, Dirk E

Sabine Leisten, MSc, Michiko K

T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production Ayako Matsuki, MD, Hiroaki Takatori, MD,

Prostaglandin E2 suppresses staphylococcal enterotoxin–induced eosinophilia- associated cellular responses dominantly through an E-prostanoid 2–mediated.

Fibronectin is a TH1-specific molecule in human subjects

T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production Ayako Matsuki, MD, Hiroaki Takatori, MD,

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

IL-13 mediates IL-33–dependent mast cell and type 2 innate lymphoid cell effects on bronchial epithelial cells Deepti R. Nagarkar, PhD, Vladimir Ramirez-Carrozzi,

Prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk Luzheng Xue, PhD, Joannah Fergusson,

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

Ganglioside GQ1b enhances Ig production by human PBMCs

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

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

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

Eosinophil production of prostaglandin D2 in patients with aspirin-exacerbated respiratory disease Xin Feng, MD, Madison K. Ramsden, BS, Julie Negri,

Acquisition and alteration of adhesion molecules during cultured human mast cell differentiation Hiroshi Tachimoto, MD, PhD, Sherry A. Hudson, MSB, Bruce.

D-type prostanoid receptor enhances the signaling of chemoattractant receptor– homologous molecule expressed on TH2 cells Miriam Sedej, MSc, Ralf Schröder,

Sachin K. Samuchiwal, PhD, Joshua A. Boyce, MD

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

Fevipiprant, a selective prostaglandin D2 receptor 2 antagonist, inhibits human group 2 innate lymphoid cell aggregation and function Clare Hardman,

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

IL-10, TGF-β, and glucocorticoid prevent the production of type 2 cytokines in human group 2 innate lymphoid cells Noriko Ogasawara, MD, PhD, Julie A.

Toll-like receptor agonists differentially regulate cysteinyl-leukotriene receptor 1 expression and function in human dendritic cells Maryse Thivierge,

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

Lung type 2 innate lymphoid cells express cysteinyl leukotriene receptor 1, which regulates TH2 cytokine production Taylor A. Doherty, MD, Naseem Khorram,

IL-10–producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients Antje Prasse, MD, Martin Germann,

Autocrine-regulated airway smooth muscle cell migration is dependent on IL-17–induced growth-related oncogenes Laila A. Al-Alwan, PhD, Ying Chang, PhD,

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

Reciprocal regulation of cultured human mast cell cytokine production by IL-4 and IFN-γ Hiroshi Tachimoto, MD, PhDa, Motohiro Ebisawa, MD, PhDa,b, Tomohide.

Thymic stromal lymphopoietin does not activate human basophils

Ramses Ilarraza, PhD, Yingqi Wu, Christopher D

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,

Presentation transcript:

Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells Luzheng Xue, PhD, Maryam Salimi, MD, Isabel Panse, BTA, Jenny M. Mjösberg, PhD, Andrew N.J. McKenzie, PhD, Hergen Spits, PhD, Paul Klenerman, F Med Sci, Graham Ogg, DPhil, FRCP Journal of Allergy and Clinical Immunology Volume 133, Issue 4, Pages 1184-1194.e7 (April 2014) DOI: 10.1016/j.jaci.2013.10.056 Copyright © 2013 The Authors Terms and Conditions

Fig 1 ILC2 isolation. ILC2s isolated from human skin were lineage marker–negative (CD3, CD4, CD8, CD14, CD19, CD56, CD11c, CD11 b, FcεRI, T-cell receptor γδ, T-cell receptor αβ, and CD123), CD45high, IL-7Rα+, and CRTH2+. Isotype controls are shown in Fig E1. Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig 2 Migration of ILC2s (A and B, skin; C, blood) to PGD2 is mediated by CRTH2. Fig 2, A, Migration after stimulation with IL-25, IL-33, or PGD2. Fig 2, B, Migration after exposure to PGD2 in the absence or presence of TM30089. Fig 2, C, Migration in response to PGD2, IL-33, or IL-25 alone or in combination with or without TM30089. *P < .05 (n = 3). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig 3 CRTH2 mediates type 2 cytokine production in ILC2s (skin) in response to PGD2. A, mRNA levels of cytokines in cells (mRNA) and cytokine concentrations in supernatants (protein) after incubation with various concentration of PGD2. B, Concentrations of cytokines released after treatments are as indicated. *P < .05 between control and other treatments and **P < .05 between PGD2 and indicated treatments (n = 3). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig 4 Activation of CRTH2 evokes proinflammatory cytokine production in ILC2s (skin). A, Cytokine concentrations after stimulation with PGD2. B, mRNA levels of cytokines (mRNA) and concentrations of cytokines (protein) after treatments, as indicated. C, mRNA level of IFN-γ after treatments. *P < .05 between control and other treatments and **P < .05 between PGD2 and indicated treatments (n = 3). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig 5 Activation of CRTH2 modulates receptor expression in ILC2s (A, blood; B and C, skin). Fig 5, A, mRNA levels of receptor genes after treatments (n = 3). The expression of ST2 (Fig 5, B) and CRTH2 (Fig 5, C) in ILC2s after incubation with medium or PGD2 with or without TM30089 for 4 (Fig 5, B) or 6 (Fig 5, C) hours, as determined by using fluorescence-activated cell sorting, is shown. Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig 6 Effect of mast cell supernatants on activation of ILC2s (skin) is mediated by CRTH2. A, Levels of PGD2 and IL-13 in supernatants of mast cells treated with medium (white bars) or IgE/anti-IgE antibody with (black bars) or without (gray bars) diclofenac. Supernatants were assigned as supernatants 1 to 3. B, ILC2 migration after exposure to supernatants with or without TM30089. C and D, mRNA and protein levels of cytokines (Fig 6, C) and mRNA levels of receptors (Fig 6, D) in ILCs after incubation with supernatants with or without TM30089 for 3 hours. *P < .05 (n = 2). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig E1 Isotype controls for ILC2 isolation (Fig 1). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig E2 Comparison of Lin−CD127+CRTH2− and Lin−CD127+CRTH2+ cells from human skin. A, Expression of ST2 (blue line) on CRTH2− cells was much lower than expression on CRTH2+ cells. The red line shows unstained cells. B, Lin−CD127+CRTH2+ (white columns) but not Lin−CD127+CRTH2- cells (black columns) responded to IL-33 stimulation by IL-13 production (n = 2). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig E3 Expression of ST2, IL-17RA, and CRTH2 in ILC2s (skin) is regulated by PGD2 in a dose-dependent manner. The mRNA level of ST2, CRTH2, IL-17RA, and IL-17RB in the cell pellets of ILC2s after stimulation with various concentrations of PGD2 is shown. The mRNA levels in the cells treated with 1 nmol/L PGD2 were treated as 1-fold (n = 2). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig E4 CRTH2 mediates proinflammatory cytokine production in ILC2s (skin) in response to supernatants from activated mast cells. Concentrations of IL-3, IL-8, IL-9, IL-21, GM-CSF, and CSF-1 in supernatants after ILC2 incubation with 1:1.5 diluted supernatants of mast cells treated with medium (white bars) or IgE/anti-IgE antibody with (black bars) or without (gray bars) diclofenac in the presence or absence of TM30089 for 3 hours. *P < .05 (n = 2). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions

Fig E5 Cytokine production by ILC2s (skin) in response to supernatants from activated mast cells is inhibited by CysLT1 antagonist partially but not by D prostanoid receptor antagonist. The effects of TM30089, BWA868C, montelukast, and their combination on the production of IL-13 (protein), IL-3, and GM-CSF (mRNA) in ILC2s treated with the supernatant from IgE/anti-IgE-activated mast cells (gray bars) were examined with ELISA or quantitative RT-PCR (n = 1). Journal of Allergy and Clinical Immunology 2014 133, 1184-1194.e7DOI: (10.1016/j.jaci.2013.10.056) Copyright © 2013 The Authors Terms and Conditions