Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit.

Slides:

Advertisements

Similar presentations

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy Erik Wambre, PhD, Jonathan.

Advertisements

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

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers Thomas X. Lu,

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

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit.

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

Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders Annick A.J.M.

The importance of being “pure” neutrophils

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy Yin Yao, MD, Cai-Ling.

Asthma inflammatory phenotypes show differential microRNA expression in sputum Tania Maes, PhD, Francisco Avila Cobos, MSc, Florence Schleich, MD, PhD,

Repeated FcεRI triggering reveals modified mast cell function related to chronic allergic responses in tissue Jolien Suurmond, MSc, Kim L.L. Habets,

Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures Jelle de Wit, PhD, Tineke Jorritsma,

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers Thomas X. Lu,

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome

Distinct endotypes of steroid-resistant asthma characterized by IL-17Ahigh and IFN- γhigh immunophenotypes: Potential benefits of calcitriol Emma S. Chambers,

Rapid recruitment of CD14+ monocytes in experimentally induced allergic rhinitis in human subjects Ibon Eguíluz-Gracia, MD, Anthony Bosco, PhD, Ralph.

Type 3 innate lymphoid cells induce proliferation of CD94+ natural killer cells Shuo Li, PhD, Hideaki Morita, MD, PhD, Beate Rückert, Sci Tec, Tadech.

Birch pollen immunotherapy results in long-term loss of Bet v 1–specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies

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

Circulating innate lymphoid cells are differentially regulated in allergic and nonallergic subjects Vincent Lombardi, PhD, Chloé Beuraud, MSc, Catherine.

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

Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells Sofi Johansson, MSc, Göran Wennergren, MD, PhD, Nils Åberg,

Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway Isabelle Dupin,

Direct monitoring of basophil degranulation by using avidin-based probes Régis Joulia, PhD, Claire Mailhol, MD, Salvatore Valitutti, MD, Alain Didier,

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

Katherine G. MacDonald, BSc, Nicholas A. J

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

Expression of FcɛRI on dendritic cell subsets in peripheral blood of patients with atopic dermatitis and allergic asthma Inge M.J. Beeren, MSc, Marjolein.

Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy Kathryn E. Hulse, BS, Amanda J. Reefer, MS, Victor.

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

Profiling of human CD4+ T-cell subsets identifies the TH2-specific noncoding RNA GATA3-AS1 Huan Zhang, MD, PhD, Colm E. Nestor, PhD, Shuli Zhao, PhD,

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,

Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible.

Allison K. Martin, BS, Douglas G. Mack, PhD, Michael T

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

Benjamin T. Prince, MD, Msci, Ashley L. Devonshire, MD, MPH, Kristin A

Chronic cat allergen exposure induces a TH2 cell–dependent IgG4 response related to low sensitization Amedee Renand, PhD, Luis D. Archila, MSc, John.

Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors Donald W. MacGlashan, MD, PhD,

Decreases in human dendritic cell–dependent TH2-like responses after acute in vivo IgE neutralization John T. Schroeder, PhD, Anja P. Bieneman, BS, Kristin.

Role of IL-35 in sublingual allergen immunotherapy

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

Human Inflammatory Dendritic Cells Induce Th17 Cell Differentiation

The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting.

Allergen-specific immunotherapy with recombinant grass pollen allergens Marek Jutel, MD, Lothar Jaeger, MD, Roland Suck, PhD, Hanns Meyer, Dipl Math,

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy Erik Wambre, PhD, Jonathan.

Characterization of ζ-associated protein, 70 kd (ZAP70)–deficient human lymphocytes Chaim M. Roifman, MD, Harjit Dadi, PhD, Raz Somech, MD, Amit Nahum,

IL-9 is a key component of memory TH cell peanut-specific responses from children with peanut allergy Helen A. Brough, MSc, FRCPCH, David J. Cousins,

IL-2– and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets Sven Létourneau, DPhil, Carsten Krieg, PhD, Giuseppe Pantaleo,

Allergen-specific CD8+ T cells in peanut-allergic individuals

Live and heat-treated probiotics differently modulate IL10 mRNA stabilization and microRNA expression Audrey Demont, BS, Feriel Hacini-Rachinel, PhD,

Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy Véronique Schulten, PhD,

CD23 surface density on B cells is associated with IgE levels and determines IgE- facilitated allergen uptake, as well as activation of allergen-specific.

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

Allergen-specific immunotherapy modulates the balance of circulating Tfh and Tfr cells Véronique Schulten, PhD, Victoria Tripple, BSc, Grégory Seumois,

The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting.

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

Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders Annick A.J.M.

CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X- linked–like syndrome, and defective IL-10 expression from CD4 lymphocytes

A flow cytometry–based diagnosis of eosinophilic esophagitis

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

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

Karl J. Staples, PhD, Timothy S. C. Hinks, MB BS, Jon A

Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding Sven.

Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells Yifang Gao, PhD, Sarita Workman, MSc,

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

Perturbations of natural killer cell regulatory functions in respiratory allergic diseases Francesca Scordamaglia, MD, Mirna Balsamo, PhD, Antonio Scordamaglia,

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

Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin Soma.

Der p 1–induced CD4+FOXP3+GATA3+ T cells have suppressive properties and contribute to the polarization of the TH2-associated response Lieke Reubsaet,

Presentation transcript:

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy Claire Gueguen, PhD, Julien Bouley, PhD, Hélène Moussu, MSc, Sonia Luce, MSc, Magalie Duchateau, PhD, Julia Chamot-Rooke, PhD, Marc Pallardy, PhD, Vincent Lombardi, PhD, Emmanuel Nony, PhD, Véronique Baron-Bodo, PhD, Laurent Mascarell, PhD, Philippe Moingeon, PhD Journal of Allergy and Clinical Immunology Volume 137, Issue 2, Pages 545-558 (February 2016) DOI: 10.1016/j.jaci.2015.09.015 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Characterization of DC2s in comparison with Ctrl-DCs, DC1s, and DCreg cells. A, Cytokine production was analyzed with a multiplex quantification assay (n = 12). B, qPCR analysis of genes expressed in effector and regulatory DCs (n = 6). C, Cytokine production by CD4+ T cells cultured for 5 days with DCs analyzed by using a multiplex quantification assay (n = 12). Data are shown as means ± SEMs. *P < .05, **P < .01, and ***P < .001, Wilcoxon tests. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Comparative patterns of gene expression in Ctrl-DCs, DC1s, DC2s, and DCreg cells. Hierarchically clustered heat maps display median-centered log 2 intensities (based on the analysis of 6 groups of DC subsets originating from distinct donors). A and B, Genes upregulated (red) and downregulated (green), respectively, in DC2s in comparison with DC1s, with a false discovery rate P value of less than .01 and a fold difference of 4 or greater. C, Genes upregulated (green) in DCreg cells in comparison with Ctrl-DCs, with a false discovery rate P value of less than .01 and a fold difference of 4 or greater. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Comparative patterns of gene expression in Ctrl-DCs, DC1s, DC2s, and DCreg cells. Hierarchically clustered heat maps display median-centered log 2 intensities (based on the analysis of 6 groups of DC subsets originating from distinct donors). A and B, Genes upregulated (red) and downregulated (green), respectively, in DC2s in comparison with DC1s, with a false discovery rate P value of less than .01 and a fold difference of 4 or greater. C, Genes upregulated (green) in DCreg cells in comparison with Ctrl-DCs, with a false discovery rate P value of less than .01 and a fold difference of 4 or greater. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Validation of markers associated with DC2s by using qPCR and flow cytometry. A-C, qPCR analysis of mRNAs corresponding to DC2 markers identified by using cDNA microarrays (markers upregulated [Fig 3, A] or downregulated [Fig 3, B] by DC2s) or label-free quantitative proteomics (Fig 3, C). D and E, mRNA (Fig 3, D) and cell-surface (Fig 3, E) expression of potential type 2 markers previously identified by others27-30 were assessed by using qPCR and flow cytometry, respectively, in Ctrl-DCs and polarized DCs. Results in Fig 3, E, are expressed as mean fluorescence intensities (MFI) after subtracting signals obtained with control isotype antibodies. FACS, Fluorescence-activated cell sorting. Data are shown as means ± SEMs (n = 6). *P < .05, Wilcoxon tests. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Validation of markers associated with DCreg cells by using qPCR. Expression of mRNAs corresponding to markers identified by using cDNA microarrays (A) or label-free quantitative proteomics (B) was analyzed in Ctrl-DCs and polarized DCs by using qPCR. Data are shown as means ± SEMs (n = 6). *P < .05, Wilcoxon tests. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 DC2-associated markers are downregulated after 4 months of AIT in PBMCs from patients with grass pollen allergy in relationship with clinical benefit. A, Changes after AIT in expression of CD141, GATA3, OX40L, and RIPK4 genes were assessed by using qPCR in PBMCs from patients of the active and placebo groups (ARs, n = 21; ANRs, n = 21; placebo responders [PR], n = 7; and placebo nonresponders [PNR], n = 31). *P < .05, **P < .01, and ***P < .001, Mann-Whitney tests. B, Spearman correlation at an individual patient level of changes after AIT in the expression of CD141, GATA3, OX40L, and RIPK4 genes with percentage improvements in ARTSSs (visit 7/visit 3) in patients from the active and placebo groups. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 DCreg cell–associated markers are upregulated after 4 months of AIT in PBMCs from patients with grass pollen allergy in relationship with clinical benefit. A, Changes after AIT in expression of C1QA, FcγRIIIA, FTL, and SLCO2B1 genes were assessed by using qPCR in PBMCs from patients of the active and placebo groups. *P < .05, **P < .01, and ***P < .001, Mann-Whitney test. B, Spearman correlations at the individual patient level of changes after AIT in expression of C1QA, FcγRIIIA, FTL, and SLCO2B1 mRNAs with percentage improvement in ARTSSs (visit 7/visit 3) in patients from the active and placebo groups. C, Spearman correlations of changes after 4 months of AIT in gene expression in patients from the active group (n = 42). PNR, Placebo nonresponders; PR, placebo responders. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 Changes in expression of 5 combined DCreg/DC2–associated markers in PBMCs from patients with grass pollen allergy correlate with clinical efficacy after 2 and 4 months of AIT. ROC analyses of a combination of 3 DC2-associated markers (CD141, GATA3, and RIPK4) and 2 DCreg-associated markers (C1QA and FcγRIIIA) after 2 months of AIT (A) and 4 months of AIT (B). Spearman correlations at the individual patient level of changes in expression of the 5 combined markers with percentages of ARTSS improvement in patients from the active and placebo groups after 2 months (C) and 4 months (D) of AIT. AUC, Area under the ROC curve; PNR, placebo nonresponders; PR, placebo responders. *P < .05 and ***P < .001. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 8 Alterations in DCreg/DC2–associated markers are induced during AIT in both patients with and those without allergen-specific antibody responses. Correlation between changes after 4 months of AIT in expression of the 5 combined DCreg/DC2 markers and percentages of ARTSS improvement in patients from the active group, comprising both immunoreactive (ie, exhibiting strong allergen-specific antibody responses, black dots) and nonimmunoreactive (ie, exhibiting no or low allergen-specific antibody responses, open dots) patients. Journal of Allergy and Clinical Immunology 2016 137, 545-558DOI: (10.1016/j.jaci.2015.09.015) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions