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[PMID]:28796044
[Au] Autor:Chen J; Li JH; Zhao SJ; Wang DY; Zhang WZ; Liang WJ
[Ad] Endereço:aDepartment of Cardiovascular Medicine, Guangzhou Panyu Central Hospital, bPanyu District Cardiovascular Disease Research Institute of Guangzhou, Guangzhou, P.R. China.
[Ti] Título:Clinical significance of costimulatory molecules CD40/CD40L and CD134/CD134L in coronary heart disease: A case-control study.
[So] Source:Medicine (Baltimore);96(32):e7634, 2017 Aug.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of the study was to evaluate the potential role of CD40/CD40 ligand (CD40L) and CD134/CD134 ligand (CD134L) in the development of coronary heart disease (CHD) via the performance of a case-control study.The research objects were 234 cases of CHD patients and 120 cases of well-matched normal controls. Following the separation of peripheral blood mononuclear cells (PBMCs), real-time quantitative PCR (qRT-PCR), Western blot, immunohistochemistry, and flow cytometry were applied for the detection of mRNA levels and expression levels of CD40/CD40L and CD134/CD134L; meanwhile, intercellular adhesion molecule-1 (ICAM-1) and Fas protein mRNA levels were detected using qRT-PCR.There was no statistical difference in the comparison of baseline characteristics between groups, indicating comparability between groups. qRT-PCR and Western blot analysis indicated that CD40/CD40L and CD134/CD134L mRNA and protein expression levels were all increased in the CHD group than those in the control group. Flow cytometry further confirmed the similar tendency. Meanwhile, ICAM-1 and Fas protein mRNA levels were elevated in the CHD group and positively correlated with the above parameters. Furthermore, CD40/CD40L expression rates were negatively correlated with gender and different types of CHD. Meanwhile, CD134/CD134L expressions were also higher in male patients, in patients with family history, previous history of hypertension, diabetes, and cerebrovascular diseases.CD40/CD40L and CD134/CD134L are increased and may have potential correlation with clinical pathological features of patients with CHD. Further in-depth exploration of costimulatory molecules for CHD guidance as well as intrinsic mechanisms are needed combined with in vivo and in vitro experiments.
[Mh] Termos MeSH primário: Antígenos CD40/biossíntese
Ligante de CD40/biossíntese
Doença das Coronárias/fisiopatologia
Ligante OX40/biossíntese
Receptores OX40/biossíntese
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Casos e Controles
Feminino
Citometria de Fluxo
Seres Humanos
Molécula 1 de Adesão Intercelular/biossíntese
Masculino
Meia-Idade
RNA Mensageiro
Reação em Cadeia da Polimerase em Tempo Real
Receptor fas/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (CD40 Antigens); 0 (FAS protein, human); 0 (OX40 Ligand); 0 (RNA, Messenger); 0 (Receptors, OX40); 0 (fas Receptor); 126547-89-5 (Intercellular Adhesion Molecule-1); 147205-72-9 (CD40 Ligand)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007634


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[PMID]:28566332
[Au] Autor:Jiang H; Rivera-Molina Y; Gomez-Manzano C; Clise-Dwyer K; Bover L; Vence LM; Yuan Y; Lang FF; Toniatti C; Hossain MB; Fueyo J
[Ad] Endereço:Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas. hjiang@mdanderson.org jfueyo@mdanderson.org.
[Ti] Título:Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination.
[So] Source:Cancer Res;77(14):3894-3907, 2017 Jul 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor, and reactivate antitumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune costimulator OX40 ligand (OX40L). Like its predecessor Delta-24-RGD, Delta-24-RGDOX induced immunogenic cell death and recruit lymphocytes to the tumor site. Compared with Delta-24-RGD, Delta-24-RGDOX exhibited superior tumor-specific activation of lymphocytes and proliferation of CD8 T cells specific to tumor-associated antigens, resulting in cancer-specific immunity. Delta-24-RGDOX mediated more potent antiglioma activity in immunocompetent C57BL/6 but not immunodeficient athymic mice, leading to specific immune memory against the tumor. To further overcome the immune suppression mediated by programmed death-ligand 1 (PD-L1) expression on cancer cells accompanied with virotherapy, intratumoral injection of Delta-24-RGDOX and an anti-PD-L1 antibody showed synergistic inhibition of gliomas and significantly increased survival in mice. Our data demonstrate that combining an oncolytic virus with tumor-targeting immune checkpoint modulators elicits potent autologous cancer vaccination, resulting in an efficacious, tumor-specific, and long-lasting therapeutic effect. .
[Mh] Termos MeSH primário: Vacinas Anticâncer/farmacologia
Neoplasias/terapia
Terapia Viral Oncolítica/métodos
Vírus Oncolíticos/fisiologia
[Mh] Termos MeSH secundário: Células A549
Animais
Antígeno B7-H1/antagonistas & inibidores
Antígeno B7-H1/imunologia
Linfócitos T CD8-Positivos/imunologia
Linhagem Celular Tumoral
Glioma/imunologia
Glioma/terapia
Glioma/virologia
Células HEK293
Seres Humanos
Imunomodulação
Neoplasias Pulmonares/imunologia
Neoplasias Pulmonares/terapia
Neoplasias Pulmonares/virologia
Melanoma Experimental/imunologia
Melanoma Experimental/terapia
Melanoma Experimental/virologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Nus
Neoplasias/imunologia
Neoplasias/virologia
Ligante OX40/biossíntese
Ligante OX40/genética
Ligante OX40/imunologia
Vírus Oncolíticos/genética
Vírus Oncolíticos/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Cancer Vaccines); 0 (OX40 Ligand)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-17-0468


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[PMID]:28476436
[Au] Autor:Teos LY; Alevizos I
[Ad] Endereço:Sjögren's Syndrome and Salivary Gland Dysfunction Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
[Ti] Título:Genetics of Sjögren's syndrome.
[So] Source:Clin Immunol;182:41-47, 2017 Sep.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pathogenesis of Sjögren's syndrome has not been elucidated. There has been evidence that genetics play an important role in the development of this disease from earlier studies. However, till now only a number of genes have been identified to be associated with SS, and these have only a weak or moderate effect. In this review we summarize the findings of the genetics studies and emphasize the need of large multicenter projects that will increase the sample sizes to provide more meaningful associations, as is the case in other common autoimmune diseases.
[Mh] Termos MeSH primário: Antígenos HLA/genética
Síndrome de Sjogren/genética
[Mh] Termos MeSH secundário: Fator Ativador de Células B/genética
Quimiocina CCL11/genética
Proteínas de Ligação a DNA/genética
Predisposição Genética para Doença
Estudo de Associação Genômica Ampla
Seres Humanos
Fatores Reguladores de Interferon/genética
Subunidade p35 da Interleucina-12/genética
Linfotoxina-alfa/genética
Receptor 3 Desencadeador da Citotoxicidade Natural/genética
Ligante OX40/genética
Receptores CXCR5/genética
Fator de Transcrição STAT4/genética
Proteínas da Membrana Plasmática de Transporte de Serotonina/genética
Transativadores/genética
Fatores de Transcrição TFII/genética
Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
Quinases da Família src/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (B-Cell Activating Factor); 0 (CCL11 protein, human); 0 (CXCR5 protein, human); 0 (Chemokine CCL11); 0 (DNA-Binding Proteins); 0 (EBF1 protein, human); 0 (GTF2I protein, human); 0 (HLA Antigens); 0 (IL12A protein, human); 0 (IRF5 protein, human); 0 (Interferon Regulatory Factors); 0 (Interleukin-12 Subunit p35); 0 (Lymphotoxin-alpha); 0 (NCR3 protein, human); 0 (Natural Cytotoxicity Triggering Receptor 3); 0 (OX40 Ligand); 0 (Receptors, CXCR5); 0 (STAT4 Transcription Factor); 0 (STAT4 protein, human); 0 (Serotonin Plasma Membrane Transport Proteins); 0 (TNFSF13B protein, human); 0 (TNFSF4 protein, human); 0 (TNIP1 protein, human); 0 (Trans-Activators); 0 (Transcription Factors, TFII); EC 2.7.10.2 (BLK protein, human); EC 2.7.10.2 (src-Family Kinases); EC 3.4.19.12 (TNFAIP3 protein, human); EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170507
[St] Status:MEDLINE


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[PMID]:28428203
[Au] Autor:Pattarini L; Trichot C; Bogiatzi S; Grandclaudon M; Meller S; Keuylian Z; Durand M; Volpe E; Madonna S; Cavani A; Chiricozzi A; Romanelli M; Hori T; Hovnanian A; Homey B; Soumelis V
[Ad] Endereço:Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale (INSERM), U932, F-75005 Paris, France vassili.soumelis@curie.fr lucia.pattarini@curie.fr.
[Ti] Título:TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand.
[So] Source:J Exp Med;214(5):1529-1546, 2017 May 01.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLP-activated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments.
[Mh] Termos MeSH primário: Citocinas/fisiologia
Células Dendríticas/fisiologia
Ligante OX40/fisiologia
Células Th2/fisiologia
[Mh] Termos MeSH secundário: Diferenciação Celular/fisiologia
Quimiocina CXCL13/metabolismo
Seres Humanos
Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo
Interleucinas/metabolismo
Receptor de Morte Celular Programada 1/metabolismo
Proteínas Proto-Oncogênicas c-bcl-6/metabolismo
Receptores CXCR5/metabolismo
Receptores Imunológicos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BCL6 protein, human); 0 (BTLA protein, human); 0 (CXCL13 protein, human); 0 (CXCR5 protein, human); 0 (Chemokine CXCL13); 0 (Cytokines); 0 (ICOS protein, human); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (Interleukins); 0 (OX40 Ligand); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 0 (Proto-Oncogene Proteins c-bcl-6); 0 (Receptors, CXCR5); 0 (Receptors, Immunologic); 0 (interleukin-21); 0 (thymic stromal lymphopoietin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20150402


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[PMID]:28335888
[Au] Autor:Dempke WCM; Fenchel K; Uciechowski P; Dale SP
[Ad] Endereço:Kyowa Kirin Pharmaceutical Development, Galashiels, United Kingdom; University of Munich, University Hospital of Grosshadern, Department of Haematology and Oncology, Germany. Electronic address: wolfram.dempke@kyowakirin.com.
[Ti] Título:Second- and third-generation drugs for immuno-oncology treatment-The more the better?
[So] Source:Eur J Cancer;74:55-72, 2017 Mar.
[Is] ISSN:1879-0852
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and ß-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations). To improve response rates and to overcome resistance, novel second- and third-generation immuno-oncology drugs are currently evaluated in ongoing phase I/II trials (either alone or in combination) including novel inhibitory compounds (e.g. TIM-3, VISTA, LAG-3, IDO, KIR) and newly developed co-stimulatory antibodies (e.g. CD40, GITR, OX40, CD137, ICOS). It is important to note that co-stimulatory agents strikingly differ in their proposed mechanism of action compared with monoclonal antibodies that accomplish immune activation by blocking negative checkpoint molecules such as CTLA-4 or PD-1/PD-1 or others. Indeed, the prospect of combining agonistic with antagonistic agents is enticing and represents a real immunologic opportunity to 'step on the gas' while 'cutting the brakes', although this strategy as a novel cancer therapy has not been universally endorsed so far. Concerns include the prospect of triggering cytokine-release syndromes, autoimmune reactions and hyper immune stimulation leading to activation-induced cell death or tolerance, however, toxicity has not been a major issue in the clinical trials reported so far. Although initial phase I/II clinical trials of agonistic and novel antagonistic drugs have shown highly promising results in the absence of disabling toxicity, both in single-agent studies and in combination with chemotherapy or other immune system targeting drugs; however, numerous questions remain about dose, schedule, route of administration and formulation as well as identifying the appropriate patient populations. In our view, with such a wealth of potential mechanisms of action and with the ability to fine-tune monoclonal antibody structure and function to suit particular requirements, the second and third wave of immuno-oncology drugs are likely to provide rapid advances with new combinations of novel immunotherapy (especially co-stimulatory antibodies). Here, we will review the mechanisms of action and the clinical data of these new antibodies and discuss the major issues facing this rapidly evolving field.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/uso terapêutico
Antineoplásicos/uso terapêutico
Imunoterapia/métodos
Neoplasias/terapia
[Mh] Termos MeSH secundário: Antígenos CD/efeitos dos fármacos
Linfócitos B/imunologia
Antígenos B7/antagonistas & inibidores
Antígenos B7/imunologia
Antígenos CD40/agonistas
Antígeno CTLA-4/antagonistas & inibidores
Citocinas/imunologia
Proteína Relacionada a TNFR Induzida por Glucocorticoide/efeitos dos fármacos
Receptor Celular 2 do Vírus da Hepatite A/antagonistas & inibidores
Seres Humanos
Imunidade Celular/fisiologia
Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores
Proteína Coestimuladora de Linfócitos T Induzíveis/agonistas
Células Matadoras Naturais/imunologia
Ativação Linfocitária/imunologia
Complexo Principal de Histocompatibilidade/imunologia
Neoplasias/imunologia
Ligante OX40/agonistas
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptores KIR/antagonistas & inibidores
Subpopulações de Linfócitos T/imunologia
Linfócitos T Citotóxicos/imunologia
Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD); 0 (Antineoplastic Agents); 0 (B7 Antigens); 0 (CD223 antigen); 0 (CD40 Antigens); 0 (CTLA-4 Antigen); 0 (Cytokines); 0 (Glucocorticoid-Induced TNFR-Related Protein); 0 (HAVCR2 protein, human); 0 (Hepatitis A Virus Cellular Receptor 2); 0 (ICOS protein, human); 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (OX40 Ligand); 0 (Programmed Cell Death 1 Receptor); 0 (Receptors, KIR); 0 (TNFRSF18 protein, human); 0 (TNFRSF9 protein, human); 0 (TNFSF4 protein, human); 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9); 0 (VISTA protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


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[PMID]:28320444
[Au] Autor:Jiang J; Liu C; Liu M; Shen Y; Hu X; Wang Q; Wu J; Wu M; Fang Q; Zhang X
[Ad] Endereço:Jiangsu Institute of Clinical Immunology & Jiangsu Key Laboratory of Clinical Immunology, First Affiliated Hospital of Soochow University, No. 708 Renmin Road, Suzhou, 215006, Jiangsu, China.
[Ti] Título:OX40 signaling is involved in the autoactivation of CD4 CD28 T cells and contributes to the pathogenesis of autoimmune arthritis.
[So] Source:Arthritis Res Ther;19(1):67, 2017 Mar 21.
[Is] ISSN:1478-6362
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: CD4 CD28 T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of this study was to investigate the costimulatory effects of OX40 on CD4 CD28 T cells in autoimmune arthritis. METHODS: Clinical samples were collected from patients with RA and control subjects. Collagen-induced arthritis (CIA) was induced with collagen type II (CII) in DBA/1 mice. The CD4 CD28 OX40 T-cell subset and its cytokine production were detected by flow cytometry. After T-cell purification, adoptive transfer was performed in CIA mice. The regulatory role of OX40 was determined by blocking experiments in vitro and in vivo. RESULTS: OX40 and OX40L were abnormally expressed in patients with RA and CIA mice. Further analysis showed that CD4 CD28 OX40 T cells accumulated in patients with RA and in animal models. These cells produced higher levels of proinflammatory cytokines and were closely correlated with the clinicopathological features of the affected individuals. Adoptive transfer of CII-specific CD4 CD28 OX40 T cells remarkably aggravated arthritic development and joint pathology in CIA mice. Moreover, OX40 blockade significantly reduced the proinflammatory responses and ameliorated arthritis development. CONCLUSIONS: OX40 acts as an alternative costimulator of CD4 CD28 T cells and plays a pathogenic role in autoimmune arthritic development, suggesting that it is a potential target for immunomodulatory therapy of RA.
[Mh] Termos MeSH primário: Artrite Reumatoide/imunologia
Linfócitos T CD4-Positivos/imunologia
Ativação Linfocitária/imunologia
Receptores OX40/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Artrite Experimental/imunologia
Feminino
Citometria de Fluxo
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos DBA
Ligante OX40/imunologia
Transdução de Sinais/imunologia
Subpopulações de Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (OX40 Ligand); 0 (Receptors, OX40)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1186/s13075-017-1261-9


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[PMID]:28275260
[Au] Autor:Croft M; Siegel RM
[Ad] Endereço:Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, and Department of Medicine, University of California San Diego, La Jolla, California 92037, USA.
[Ti] Título:Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases.
[So] Source:Nat Rev Rheumatol;13(4):217-233, 2017 Apr.
[Is] ISSN:1759-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:TNF blockers are highly efficacious at dampening inflammation and reducing symptoms in rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and also in nonrheumatic syndromes such as inflammatory bowel disease. As TNF belongs to a superfamily of 19 structurally related proteins that have both proinflammatory and anti-inflammatory activity, reagents that disrupt the interaction between proinflammatory TNF family cytokines and their receptors, or agonize the anti-inflammatory receptors, are being considered for the treatment of rheumatic diseases. Biologic agents that block B cell activating factor (BAFF) and receptor activator of nuclear factor-κB ligand (RANKL) have been approved for the treatment of systemic lupus erythematosus and osteoporosis, respectively. In this Review, we focus on additional members of the TNF superfamily that could be relevant for the pathogenesis of rheumatic disease, including those that can strongly promote activity of immune cells or increase activity of tissue cells, as well as those that promote death pathways and might limit inflammation. We examine preclinical mouse and human data linking these molecules to the control of damage in the joints, muscle, bone or other tissues, and discuss their potential as targets for future therapy of rheumatic diseases.
[Mh] Termos MeSH primário: Terapia de Alvo Molecular
Doenças Reumáticas/tratamento farmacológico
Doenças Reumáticas/imunologia
Fatores de Necrose Tumoral/antagonistas & inibidores
Fatores de Necrose Tumoral/metabolismo
[Mh] Termos MeSH secundário: Ligante 4-1BB/antagonistas & inibidores
Ligante 4-1BB/metabolismo
Animais
Ligante CD27/antagonistas & inibidores
Ligante CD27/metabolismo
Ligante de CD40/antagonistas & inibidores
Ligante de CD40/metabolismo
Morte Celular
Citocina TWEAK
Células Dendríticas/imunologia
Proteína Ligante Fas/antagonistas & inibidores
Proteína Ligante Fas/metabolismo
Seres Humanos
Tolerância Imunológica
Ativação Linfocitária
Linfotoxina-alfa/antagonistas & inibidores
Linfotoxina-alfa/metabolismo
Ligante OX40/antagonistas & inibidores
Ligante OX40/metabolismo
Transdução de Sinais
Linfócitos T/imunologia
Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidores
Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/antagonistas & inibidores
Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/antagonistas & inibidores
Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
Fatores de Necrose Tumoral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (4-1BB Ligand); 0 (CD27 Ligand); 0 (Cytokine TWEAK); 0 (Fas Ligand Protein); 0 (Lymphotoxin-alpha); 0 (OX40 Ligand); 0 (TNF-Related Apoptosis-Inducing Ligand); 0 (TNFSF12 protein, human); 0 (TNFSF18 protein, human); 0 (Tumor Necrosis Factor Ligand Superfamily Member 14); 0 (Tumor Necrosis Factor Ligand Superfamily Member 15); 0 (Tumor Necrosis Factors); 147205-72-9 (CD40 Ligand)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.1038/nrrheum.2017.22


  8 / 320 MEDLINE  
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[PMID]:28092803
[Au] Autor:Willoughby J; Griffiths J; Tews I; Cragg MS
[Ad] Endereço:Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.
[Ti] Título:OX40: Structure and function - What questions remain?
[So] Source:Mol Immunol;83:13-22, 2017 Mar.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OX40 is a type 1 transmembrane glycoprotein, reported nearly 30 years ago as a cell surface antigen expressed on activated T cells. Since its discovery, it has been validated as a bone fide costimulatory molecule for T cells and member of the TNF receptor family. However, many questions still remain relating to its function on different T cell sub-sets and with recent interest in its utility as a target for antibody-mediated immunotherapy, there is a growing need to gain a better understanding of its biology. Here, we review the expression pattern of OX40 and its ligand, discuss the structure of the receptor:ligand interaction, the downstream signalling it can elicit, its function on different T cell subsets and how antibodies might engage with it to provide effective immunotherapy.
[Mh] Termos MeSH primário: Ligante OX40/imunologia
Receptores OX40/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Ativação Linfocitária/imunologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (OX40 Ligand); 0 (Receptors, OX40)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE


  9 / 320 MEDLINE  
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[PMID]:28074529
[Au] Autor:Cacan E
[Ad] Endereço:Department of Molecular Biology Genetics, Gaziosmanpasa University, Tokat, 60250, Turkey.
[Ti] Título:Epigenetic-mediated immune suppression of positive co-stimulatory molecules in chemoresistant ovarian cancer cells.
[So] Source:Cell Biol Int;41(3):328-339, 2017 Mar.
[Is] ISSN:1095-8355
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity. This study demonstrates that expression of positive co-stimulatory molecules, OX-40L and 4-1BBL, is suppressed while expression of immunosuppressive molecule programmed death ligand-1 (PD-L1/CD274) is enhanced in chemoresistant cells compared to parental chemosensitive ovarian cancer cells. Here, the molecular mechanisms of silencing of OX-40L and 4-1BBL expression were investigated in chemoresistant A2780-AD ovarian cancer cells. The suppression of OX-40L and 4-1BBL are due to DNA hypermethylation and histone deacetylation, two important mechanisms that contribute to gene silencing during cancer progression. We identify important epigenetic regulators, histone deacetylase 1/3 (HDAC1/HDAC3) and DNA methyltransferase 1 (DNMT1), that exhibit aberrant association with OX-40L and 4-1BBL promoters in chemoresistant ovarian cancer cells. Knockdown of HDAC1 or DNMT1 expression, and pharmacological inhibition of DNMT or HDAC enzymatic activity, significantly increase OX-40L and 4-1BBL expression in chemoresistant cells. This study suggests that loss of histone acetylation and accumulation of DNA methylation correlates with suppressed expression of OX-40L and 4-1BBL in chemoresistant ovarian cancer cells. This study marks the first report of the regulation of these two molecules by histone deacetylation and DNA methylation in chemoresistant ovarian cancer cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Resistência a Medicamentos Antineoplásicos/fisiologia
Epigênese Genética/fisiologia
Tolerância Imunológica/fisiologia
Neoplasias Ovarianas/imunologia
[Mh] Termos MeSH secundário: Ligante 4-1BB/biossíntese
Ligante 4-1BB/imunologia
Linhagem Celular Tumoral
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Epigênese Genética/efeitos dos fármacos
Feminino
Seres Humanos
Tolerância Imunológica/efeitos dos fármacos
Ligante OX40/biossíntese
Ligante OX40/imunologia
Neoplasias Ovarianas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-1BB Ligand); 0 (Antineoplastic Agents); 0 (OX40 Ligand); 0 (TNFSF4 protein, human)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170222
[Lr] Data última revisão:
170222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1002/cbin.10729


  10 / 320 MEDLINE  
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[PMID]:27905107
[Au] Autor:Williams AR; Klaver EJ; Laan LC; Ramsay A; Fryganas C; Difborg R; Kringel H; Reed JD; Mueller-Harvey I; Skov S; van Die I; Thamsborg SM
[Ad] Endereço:Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
[Ti] Título:Co-operative suppression of inflammatory responses in human dendritic cells by plant proanthocyanidins and products from the parasitic nematode Trichuris suis.
[So] Source:Immunology;150(3):312-328, 2017 Mar.
[Is] ISSN:1365-2567
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e.g. soluble products from the helminth parasite Trichuris suis (TsSP). We show that PAC are endocytosed by monocyte-derived DCs and selectively induce CD86 expression. Subsequently, PAC suppress the LPS-induced secretion of interleukin-6 (IL-6) and IL-12p70, while enhancing secretion of IL-10. Incubation of DCs with PAC did not affect lymphocyte proliferation; however, subsequent interferon-γ production was markedly suppressed, while IL-4 production was unaffected. The activity of PAC was confined to oligomers (degree of polymerization ≥ 4). Co-pulsing DCs with TsSP and PAC synergistically reduced secretion of tumour necrosis factor-α, IL-6 and IL-12p70 while increasing IL-10 secretion. Moreover, both TsSP and PAC alone induced Th2-associated OX40L expression in DCs, and together synergized to up-regulate OX40L. These data suggest that PAC induce an anti-inflammatory phenotype in human DCs that selectively down-regulates Th1 response in naive T cells, and that they also act cooperatively with TsSP. Our results indicate a novel interaction between dietary compounds and parasite products to influence immune function, and may suggest that combinations of PAC and TsSP can have therapeutic potential for inflammatory disorders.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Células Dendríticas/efeitos dos fármacos
Inflamação/tratamento farmacológico
Proantocianidinas/farmacologia
Células Th1/imunologia
Células Th2/imunologia
Tricuríase/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antígenos de Helmintos/imunologia
Células Cultivadas
Citocinas/metabolismo
Células Dendríticas/imunologia
Células Dendríticas/parasitologia
Quimioterapia Combinada
Seres Humanos
Inflamação/imunologia
Ativação Linfocitária
Ligante OX40/genética
Ligante OX40/metabolismo
Interferência de RNA
Suínos
Equilíbrio Th1-Th2/efeitos dos fármacos
Tricuríase/imunologia
Trichuris/imunologia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antigens, Helminth); 0 (Cytokines); 0 (OX40 Ligand); 0 (Proanthocyanidins); 0 (TNFSF4 protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE
[do] DOI:10.1111/imm.12687



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