KIR3DL2/CpG ODN Interaction Mediates Sézary Syndrome Malignant T Cell Apoptosis Bouchra Ghazi, Nicolas Thonnart, Martine Bagot, Armand Bensussan, Anne.

Slides:

Advertisements

Similar presentations

HACE1, a Potential Tumor Suppressor Gene on 6q21, Is Not Involved in Extranodal Natural Killer/T-Cell Lymphoma Pathophysiology Nouhoum Sako, Valérie.

Advertisements

MicroRNA-21 Expression in CD4+ T Cells Is Regulated by STAT3 and Is Pathologically Involved in Sézary Syndrome Leslie van der Fits, Marloes S. van Kester,

Vemurafenib Induces Senescence Features in Melanoma Cells

CD271 on Melanoma Cell Is an IFN-γ-Inducible Immunosuppressive Factor that Mediates Downregulation of Melanoma Antigens Junpei Furuta, Takashi Inozume,

CD158k Is a Reliable Marker for Diagnosis of Sézary Syndrome and Reveals an Unprecedented Heterogeneity of Circulating Malignant Cells Hélène Moins-Teisserenc,

Increased Expression of CTLA-4 in Malignant T Cells from Patients with Mycosis Fungoides – Cutaneous T-Cell Lymphoma Henry K. Wong, Adam J. Wilson, Heather.

Impaired Responses of Peripheral Blood Mononuclear Cells to Staphylococcal Superantigen in Patients with Severe Atopic Dermatitis: A Role of T Cell Apoptosis

Modification of Alternative Splicing of Mcl-1 Pre-mRNA Using Antisense Morpholino Oligonucleotides Induces Apoptosis in Basal Cell Carcinoma Cells Jeng-Jer.

Kynurenine Increases Matrix Metalloproteinase-1 and -3 Expression in Cultured Dermal Fibroblasts and Improves Scarring In Vivo Yunyuan Li, Ruhangiz T.

C-CBL E3 Ubiquitin Ligase Is Overexpressed in Cutaneous T-Cell Lymphoma: Its Inhibition Promotes Activation-Induced Cell Death Jianqiang Wu, Katrin A.

Upregulation of Inflammatory Cytokines and Oncogenic Signal Pathways Preceding Tumor Formation in a Murine Model of T-Cell Lymphoma in Skin Xuesong Wu,

FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides.

Efficient TRAIL-R1/DR4-Mediated Apoptosis in Melanoma Cells by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Bahtier M. Kurbanov, Christoph.

Activation-Dependent Modulation of Hyaluronate-Receptor Expression and of Hyaluronate-Avidity by Human Monocytes Johannes M. Weiss, Andreas C. Renkl,

Cytokine Effects Induced by the Human Autoallergen α-NAC

Phosphatidylinositol 3-Kinase/Akt-Dependent and -Independent Protection Against Apoptosis in Normal Human Melanocytes Masahiro Oka, Akiko Kageyama, Mizuho.

SDC 2 - Figure S1.

Antigen-Specific Peripheral Tolerance Induced by Topical Application of NF-κB Decoy Oligodeoxynucleotide Iwao Isomura, Kunio Tsujimura, Akimichi Morita

Interaction of HSV-1 Infected Peripheral Blood Mononuclear Cells with Cultured Dermal Microvascular Endothelial Cells: a Potential Model for the Pathogenesis.

Resistance to Activation-Induced Cell Death and Bystander Cytotoxicity Via the Fas/Fas Ligand Pathway Are Implicated in the Pathogenesis of Cutaneous.

Meghan Bliss-Moreau, Cristian Coarfa, Preethi H

Supplemental Figure % annexin V-stained cells mean A

Th2 Cytokines Increase Staphylococcus aureus Alpha Toxin–Induced Keratinocyte Death through the Signal Transducer and Activator of Transcription 6 (STAT6)

Clusterin Regulates Drug-Resistance in Melanoma Cells

Involvement of Fas (APO-1/CD-95) during Photodynamic-Therapy-Mediated Apoptosis in Human Epidermoid Carcinoma A431 Cells Nihal Ahmad, Sanjay Gupta, Denise.

IL-10-Producing Langerhans Cells and Regulatory T Cells Are Responsible for Depressed Contact Hypersensitivity in Grafted Skin Ryutaro Yoshiki, Kenji.

Enhanced Death Ligand-Induced Apoptosis in Cutaneous SCC Cells by Treatment with Diclofenac/Hyaluronic Acid Correlates with Downregulation of c-FLIP

The Selective Protein Kinase C β Inhibitor Enzastaurin Induces Apoptosis in Cutaneous T-Cell Lymphoma Cell Lines through the AKT Pathway Christiane Querfeld,

IL-18, but Not IL-12, Induces Production of IFN-γ in the Immunosuppressive Environment of HPV16 E7 Transgenic Hyperplastic Skin Christina Gosmann, Ian.

Impaired Proteasome Function Activates GATA3 in T Cells and Upregulates CTLA-4: Relevance for Sézary Syndrome Heather M. Gibson, Anjali Mishra, Derek.

CpG Oligodeoxynucleotides Prevent the Development of Scleroderma-Like Syndrome in Tight-Skin Mice by Stimulating a Th1 Immune Response Yan Shen, Motohide.

Anti-Inflammatory Activity of Sertaconazole Nitrate Is Mediated via Activation of a p38– COX-2–PGE2 Pathway Runa Sur, Jeffrey M. Babad, Michelle Garay,

Poly(I:C)-Treated Human Langerhans Cells Promote the Differentiation of CD4+ T Cells Producing IFN-γ and IL-10 Laetitia Furio, Hermine Billard, Jenny.

Antisense Targeting of cFLIP Sensitizes Activated T Cells to Undergo Apoptosis and Desensitizes Responses to Contact Dermatitis Dan V. Mourich, Jessica.

The Human Skin–Associated Autoantigen α-NAC Activates Monocytes and Dendritic Cells via TLR-2 and Primes an IL-12-Dependent Th1 Response Susanne Hradetzky,

Plexin B1 Suppresses c-Met in Melanoma: A Role for Plexin B1 as a Tumor-Suppressor Protein through Regulation of c-Met Laurel Stevens, Lindy McClelland,

Human Plasmacytoid Dendritic Cells Express Receptors for Anaphylatoxins C3a and C5a and Are Chemoattracted to C3a and C5a Ralf Gutzmer, Brigitta Köther,

Leslie van der Fits, Jacoba J. Out-Luiting, Cornelis P

David Russell, Heike Ross, E Birgitte Lane

Naoko Kanda, Shinichi Watanabe Journal of Investigative Dermatology

CD158k/KIR3DL2 Is a New Phenotypic Marker of Sezary Cells: Relevance for the Diagnosis and Follow-Up of Sezary Syndrome Ewa Poszepczynska-Guigné, Valérie.

Axl Promotes Cutaneous Squamous Cell Carcinoma Survival through Negative Regulation of Pro-Apoptotic Bcl-2 Family Members Emmanouil S. Papadakis, Monika.

Ekatherina Vassina, Martin Leverkus, Shida Yousefi, Lasse R

P38 Mitogen-Activated Protein Kinase Mediates Dual Role of Ultraviolet B Radiation in Induction of Maturation and Apoptosis of Monocyte-Derived Dendritic.

Rosiglitazone Inhibits Proliferation, Motility, and Matrix Metalloproteinase Production in Keratinocytes Narasimharao Bhagavathula, Kamalakar C. Nerusu,

CD4+ CD56+ Blastic Tumor Cells Express CD101 Molecules

Interleukin-6-Resistant Melanoma Cells Exhibit Reduced Activation of STAT3 and Lack of Inhibition of Cyclin E-Associated Kinase Activity Markus Böhm,

TNF-α and IFN-γ Are Potential Inducers of Fas-Mediated Keratinocyte Apoptosis through Activation of Inducible Nitric Oxide Synthase in Toxic Epidermal.

Human Keratinocytes Respond to Osmotic Stress by p38 Map Kinase Regulated Induction of HSP70 and HSP27 M. Garmyn, A. Pupe Journal of Investigative Dermatology

Resistance of Human Melanoma Cells Against the Death Ligand TRAIL Is Reversed by Ultraviolet-B Radiation via Downregulation of FLIP Elke Zeise, Michael.

Arsenic Induces Tumor Necrosis Factor α Release and Tumor Necrosis Factor Receptor 1 Signaling in T Helper Cell Apoptosis Hsin-Su Yu, Gwo-Shing Chen

PPARδ Is a Type 1 IFN Target Gene and Inhibits Apoptosis in T Cells

Mark A. Rovedo, Nancy L. Krett, Steven T. Rosen

CD127low/- and FoxP3+ Expression Levels Characterize Different Regulatory T-Cell Populations in Human Peripheral Blood Sandra Klein, Cosima C. Kretz,

In Vitro and In Vivo Anti-Melanoma Effects of Ciglitazone

Deficient SOCS3 and SHP-1 Expression in Psoriatic T Cells

Dysregulation of Lymphocyte Interleukin-12 Receptor Expression in Sézary Syndrome Mohamed H. Zaki, Ryan B. Shane, Yuemei Geng, Louise C. Showe, Suzanne.

Interferon-γ-Mediated Growth Regulation of Melanoma Cells: Involvement of STAT1- Dependent and STAT1-Independent Signals Anja Bosserhoff Journal of Investigative.

Serotonin Activates Human Monocytes and Prevents Apoptosis

Curcumin Selectively Induces Apoptosis in Cutaneous T-Cell Lymphoma Cell Lines and Patients’ PBMCs: Potential Role for STAT-3 and NF-κB Signaling Chunlei.

Induction of RANTES by TWEAK/Fn14 Interaction in Human Keratinocytes

Dawn Cooper, Jonathan Hales, Richard Camp

Formation of Antigenic Quinolone Photoadducts on Langerhans Cells Initiates Photoallergy to Systemically Administered Quinolone in Mice Akihiro Ohshima,

Low FAS/CD95 Expression by CTCL Correlates with Reduced Sensitivity to Apoptosis that Can Be Restored by FAS Upregulation Jianqiang Wu, Minakshi Nihal,

Interleukin-17A Promotes IgE Production in Human B Cells

Expression of Sézary Biomarkers in the Blood of Patients with Erythrodermic Mycosis Fungoides Charlotte Hurabielle, Laurence Michel, Caroline Ram-Wolff,

Deon G. Uffort, Elizabeth A. Grimm, Julie A. Ellerhorst

Cucurbitacin I Inhibits Stat3 and Induces Apoptosis in Sézary Cells

Role and Regulation of STAT3 Phosphorylation at Ser727 in Melanocytes and Melanoma Cells Masanobu Sakaguchi, Masahiro Oka, Tetsushi Iwasaki, Yasuo Fukami,

Interleukin-17 is Produced by Both Th1 and Th2 Lymphocytes, and Modulates Interferon-γ- and Interleukin-4-Induced Activation of Human Keratinocytes Cristina.

Presentation transcript:

KIR3DL2/CpG ODN Interaction Mediates Sézary Syndrome Malignant T Cell Apoptosis Bouchra Ghazi, Nicolas Thonnart, Martine Bagot, Armand Bensussan, Anne Marie-Cardine Journal of Investigative Dermatology Volume 135, Issue 1, Pages 229-237 (January 2015) DOI: 10.1038/jid.2014.286 Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Downmodulation of KIR3DL2 expression on tumoral Sézary T-cell clone upon CpG ODN-C treatment. (a) The Sézary cell line (Pno) or PBMCs from Sézary patients were left untreated (NT) or incubated in the presence of CpG ODN-C or control ODN (10 μg ml−1) for 8 or 48 hours, respectively. Cells were labeled with anti-KIR3DL2 mAb (Q66) plus FITC-conjugated goat anti-mouse IgM secondary antibodies, anti-TCRVβ-PE, -CD3-PC5, and CD4-PC7 mAbs. TCRVβ/KIR3DL2 staining corresponding to the gated CD3+CD4+ T lymphocyte population is shown. The mean fluorescence intensity (MFI) of KIR3DL2 labeling is indicated. (b) Graphical representation of KIR3DL2 MFI observed on the CD3+CD4+ T cells from Sézary patients (n=12), following incubation in medium alone (NT) or supplemented with CpG ODN-C or control ODN. *P=0.004 compared with NT condition. ODN, oligodeoxynucleotide; PBMCs, peripheral blood mononuclear cells. Journal of Investigative Dermatology 2015 135, 229-237DOI: (10.1038/jid.2014.286) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Internalization of KIR3DL2 following ODN-C treatment. Cells were left untreated (a) or incubated 6 hours in the presence of control ODN (b), ODN-C (c), or FITC-conjugated ODN-C (d). Immunolabelings were then performed using FITC–coupled ODN-C, anti-LAMP1, and/or anti-KIR3DL2 antibodies, as indicated. Scale bar=10 μm. ODN, oligodeoxynucleotide. Journal of Investigative Dermatology 2015 135, 229-237DOI: (10.1038/jid.2014.286) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 CpG ODN-C induces malignant Sézary cell apoptosis. (a) The Pno Sézary cell line was left untreated (NT) or incubated with CpG ODN-C or control ODN for 24 hours at 37 °C. Apoptotic cells were detected by 7AAD labeling. Mean±SD of four independent experiments is shown. (b) Sézary patient PBMCs were incubated with CpG ODN-C or control ODN at 37 °C. Immunolabeling was performed after 3, 7, or 10 days of incubation using anti-TCRVβ3-PE and -CD4-FITC mAb and 7AAD. (c) Graphical representation of the percentage of 7AAD–positive cells within the TCRVβ+CD4+ population of Sézary patients (n=8) after 7 days of incubation with CpG ODN-C (black) or control ODN (gray). *P=0.006. ODN, oligodeoxynucleotide; PBMCs, peripheral blood mononuclear cells. Journal of Investigative Dermatology 2015 135, 229-237DOI: (10.1038/jid.2014.286) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 CpG ODN-C–induced apoptosis is associated with caspase activation. (a) The Sézary cell line or purified CD4+ T cells (98% of which were KIR3DL2+, see Supplementary Figure S4 online) from three Sézary patients were left untreated or incubated with CpG ODN-C. Post-nuclear lysates were prepared at the indicated incubation time and processed for SDS-PAGE and immunoblotting. Blots were probed successively with anti-cleaved-caspase 7, -caspase 3, -PARP, and Erk1/2 antibodies. (b) Densitometric and statistical analyses of the results shown in a on day 7. Data show fold-changes for each protein in treated samples as compared with the corresponding NT control. ODN, oligodeoxynucleotide. Journal of Investigative Dermatology 2015 135, 229-237DOI: (10.1038/jid.2014.286) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Dephosphorylation of STAT3 upon ODN-C treatment of Sézary cells. (a) The Sézary cell line Pno or sorted CD4+ T cells from Sézary patients were treated as in Figure 4. Blots were then revealed using anti-phospho-STAT3 antibodies, dehybridized, and reprobed with STAT3 antibodies. (b) Densitometric and statistical analyses of the immunoblots shown in a. ODN, oligodeoxynucleotide; STAT3, signal transducer and activator of transcription 3. Journal of Investigative Dermatology 2015 135, 229-237DOI: (10.1038/jid.2014.286) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions