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[PMID]:29180487
[Au] Autor:Pierog PL; Zhao Y; Singh S; Dai J; Yap GS; Fitzgerald-Bocarsly P
[Ad] Endereço:Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103.
[Ti] Título: Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10.
[So] Source:J Immunol;200(1):186-195, 2018 01 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-α, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-α in response to viral stimulation. In this study, we investigated the impact of coinfection with on the innate virus-directed responses of human pDCs. Using intracellular flow cytometry and fluorescence microscopy, we determined that invaded but did not induce IFN-α or TNF-α in human pDC. However, inhibited IFN-α and TNF-α produced in response to HSV and HIV, thus functionally inactivating pDC. IFN-α production was inhibited only in cells infected by , which inhibited neither uptake of GFP-HSV nor localization of TLR9 in CD71 endosomes, directing us to investigate downstream events. Using imaging flow cytometry, we found that both and IL-10 inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN response factor 7. Blockade of IFN response factor 7 nuclear translocation and inhibition of the IFN-α response was partially reversed by a deficiency in the -derived ROP16 kinase, known to directly phosphorylate STAT3, a critical mediator of IL-10's anti-inflammatory effects. Taken together, our results indicate that suppresses pDC activation by mimicking IL-10's regulatory effects through an ROP16 kinase-dependent mechanism. Our findings further imply a convergent mechanism of inhibition of TLR signaling by and IL-10 and suggest potential negative consequences of HIV/ coinfection.
[Mh] Termos MeSH primário: Células Dendríticas/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Interleucina-10/metabolismo
Infecções Oportunistas/imunologia
Proteínas Tirosina Quinases/metabolismo
Proteínas de Protozoários/metabolismo
Toxoplasma/imunologia
Toxoplasmose/imunologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Células Cultivadas
Coinfecção
Células Dendríticas/parasitologia
Seres Humanos
Imunidade Inata
Imunomodulação
Fator Regulador 7 de Interferon/metabolismo
Interferon-alfa/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
Receptor Toll-Like 9/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (IRF7 protein, human); 0 (Interferon Regulatory Factor-7); 0 (Interferon-alpha); 0 (Protozoan Proteins); 0 (STAT3 Transcription Factor); 0 (Toll-Like Receptor 9); 0 (Tumor Necrosis Factor-alpha); 130068-27-8 (Interleukin-10); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Rop16 protein, Toxoplasma gondii)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1701045


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[PMID]:28466278
[Au] Autor:Yu X; Marshall MJE; Cragg MS; Crispin M
[Ad] Endereço:The Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, General Hospital, Southampton, SO16 6YD, UK. x.yu@soton.ac.uk.
[Ti] Título:Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering.
[So] Source:BioDrugs;31(3):151-166, 2017 Jun.
[Is] ISSN:1179-190X
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Antibody-based therapeutics has emerged as a major tool in cancer treatment. Guided by the superb specificity of the antibody variable domain, it allows the precise targeting of tumour markers. Recently, eliciting cellular effector functions, mediated by the Fc domain, has gained traction as a means by which to generate more potent antibody therapeutics. Extensive mutagenesis studies of the Fc protein backbone has enabled the generation of Fc variants that more optimally engage the Fcγ receptors known to mediate cellular effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and cellular phagocytosis. In addition to the protein backbone, the homodimeric Fc domain contains two opposing N-linked glycans, which represent a further point of potential immunomodulation, independent of the Fc protein backbone. For example, a lack of core fucose usually attached to the IgG Fc glycan leads to enhanced ADCC activity, whereas a high level of terminal sialylation is associated with reduced inflammation. Significant growth in knowledge of Fc glycosylation over the last decade, combined with advancement in genetic engineering, has empowered glyco-engineering to fine-tune antibody therapeutics. This has culminated in the approval of two glyco-engineered antibodies for cancer therapy: the anti-CCR4 mogamulizumab approved in 2012 and the anti-CD20 obinutuzumab in 2013. We discuss here the technological platforms for antibody glyco-engineering and review the current clinical landscape of glyco-engineered antibodies.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/farmacologia
Anticorpos Monoclonais/uso terapêutico
Neoplasias/tratamento farmacológico
Polissacarídeos/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/imunologia
Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos
Seres Humanos
Imunomodulação/efeitos dos fármacos
Engenharia de Proteínas/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Polysaccharides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1007/s40259-017-0223-8


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[PMID]:27771140
[Au] Autor:Artyomov MN; Sergushichev A; Schilling JD
[Ad] Endereço:Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: martyomov@wustl.edu.
[Ti] Título:Integrating immunometabolism and macrophage diversity.
[So] Source:Semin Immunol;28(5):417-424, 2016 Oct.
[Is] ISSN:1096-3618
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Macrophages are heterogeneous cells that play a key role in inflammatory and tissue reparative responses. Over the past decade it has become clear that shifts in cellular metabolism are important determinants of macrophage function and phenotype. At the same time, our appreciation of macrophage diversity in vivo has also been increasing. Factors such as cell origin and tissue localization are now recognized as important variables that influence macrophage biology. Whether different macrophage populations also have unique metabolic phenotypes has not been extensively explored. In this article, we will discuss the importance of understanding how macrophage origin can modulate metabolic programming and influence inflammatory responses.
[Mh] Termos MeSH primário: Metabolismo Energético
Imunomodulação
Macrófagos/imunologia
Macrófagos/metabolismo
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica
Seres Humanos
Ativação de Macrófagos/genética
Ativação de Macrófagos/imunologia
Macrófagos/citologia
Redes e Vias Metabólicas
Especificidade de Órgãos/genética
Especificidade de Órgãos/imunologia
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28460641
[Au] Autor:Bernardi M; Agostini F; Chieregato K; Amati E; Durante C; Rassu M; Ruggeri M; Sella S; Lombardi E; Mazzucato M; Astori G
[Ad] Endereço:Advanced Cellular Therapy Laboratory, Hematology Unit, Vicenza Hospital, Vicenza, Italy.
[Ti] Título:The production method affects the efficacy of platelet derivatives to expand mesenchymal stromal cells in vitro.
[So] Source:J Transl Med;15(1):90, 2017 May 01.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The use of fetal bovine serum (FBS) as a media supplement for the ex vivo expansion of bone-marrow derived mesenchymal stromal cells (BM-MSC) has been discouraged by regulatory agencies, due to the risk of transmitting zoonoses and to elicit immune reactions in the host once transplanted. Platelet derivatives are valid FBS substitutes due to their content of growth factors that can be released disrupting the platelets by physical methods or physiological stimuli. We compared platelet derivatives produced by freezing/thawing (platelet lysates, PL) or after CaCl activation (platelet releasate surnatant rich in growth factors, PR-SRGF) for their content in growth factors and their ability to support the ex vivo expansion of BM-MSC. METHODS: The cytokine content in the two platelet derivatives was evaluated. BM-MSC were expanded in complete medium containing 10, 7.5 and 5% PL or PR-SRGF and the cell phenotype, clonogenic capacity, immunomodulation properties and tri-lineage differentiation potential of the expanded cells in both media were investigated. RESULTS: The concentration of PDGF-AB, PDGF-AA, PDGF-BB in PR-SRGF resulted to be respectively 5.7×, 1.7× and 2.3× higher compared to PL. PR-SRGF promoted a higher BM-MSC proliferation rate compared to PL not altering BM-MSC phenotype. Colony forming efficiency of BM-MSC expanded in PR-SRGF showed a frequency of colonies significantly higher than cells expanded in PL. BM-MSC expanded in PL or PR-SRGF maintained their immunomodulatory properties against activated lymphocytes even if BM-MSC expanded in FBS performed significantly better. CONCLUSIONS: The method used to release platelet factors significantly affects the enrichment in growth factors and overall product performance. The standardization of the production process of platelet derivatives and the definition of their release criteria requires further investigation.
[Mh] Termos MeSH primário: Plaquetas/metabolismo
Técnicas de Cultura de Células/métodos
Células Mesenquimais Estromais/citologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Linhagem da Célula
Proliferação Celular
Ensaio de Unidades Formadoras de Colônias
Seres Humanos
Imunomodulação
Imunofenotipagem
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intercellular Signaling Peptides and Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1186/s12967-017-1185-9


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[PMID]:28460462
[Au] Autor:Ness N; Andersen S; Khanehkenari MR; Nordbakken CV; Valkov A; Paulsen EE; Nordby Y; Bremnes RM; Donnem T; Busund LT; Richardsen E
[Ad] Endereço:Department of Medical Biology, UiT The Arctic University of Norway, N-9037 Tromso, Norway.
[Ti] Título:The prognostic role of immune checkpoint markers programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) in a large, multicenter prostate cancer cohort.
[So] Source:Oncotarget;8(16):26789-26801, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Programmed cell death protein 1 (PD-1) and its ligand Programmed death ligand 1 (PD-L1) have gained massive attention in cancer research due to recent availability and their targeted antitumor effects. Their role in prostate cancer is still undetermined. We constructed tissue microarrays from prostatectomy specimens from 535 prostate cancer patients. Following validation of antibodies, immunohistochemistry was used to evaluate the expression of PD-1 in lymphocytes and PD-L1 in epithelial and stromal cells of primary tumors. PD-L1 expression was commonly seen in tumor epithelial cells (92% of cases). Univariate survival analysis revealed a positive association between a high density of PD-1+ lymphocytes and worse clinical failure-free survival, limited to a trend (p = 0.084). In subgroups known to indicate unfavorable prostate cancer prognosis (Gleason grade 9, age < 65, preoperative PSA > 10, pT3) patients with high density of PD-1+ lymphocytes had a significantly higher risk of clinical failure (p = < 0.001, p = 0.025, p = 0.039 and p = 0.011, respectively). In the multivariate analysis, high density of PD-1+ lymphocytes was a significant negative independent prognostic factor for clinical failure-free survival (HR = 2.48, CI 95% 1.12-5.48, p = 0.025).
[Mh] Termos MeSH primário: Antígeno B7-H1/metabolismo
Biomarcadores Tumorais
Imunomodulação
Receptor de Morte Celular Programada 1/metabolismo
Neoplasias da Próstata/imunologia
Neoplasias da Próstata/metabolismo
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Fibroblastos Associados a Câncer/metabolismo
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem
Linfócitos do Interstício Tumoral/imunologia
Linfócitos do Interstício Tumoral/metabolismo
Masculino
Meia-Idade
Gradação de Tumores
Estadiamento de Neoplasias
Prognóstico
Neoplasias da Próstata/mortalidade
Neoplasias da Próstata/patologia
Reprodutibilidade dos Testes
Análise Serial de Tecidos
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15817


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[PMID]:27778165
[Au] Autor:Bai M; Liu H; Xu K; Oso AO; Wu X; Liu G; Tossou MC; Al-Dhabi NA; Duraipandiyan V; Xi Q; Yin Y
[Ad] Endereço:Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, 410125, Hunan, China.
[Ti] Título:A review of the immunomodulatory role of dietary tryptophan in livestock and poultry.
[So] Source:Amino Acids;49(1):67-74, 2017 01.
[Is] ISSN:1438-2199
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Tryptophan, a nutritionally essential amino acid, is active in the regulation of immune responses in animals. The products of tryptophan metabolism, such as indoleamine 2,3-dioxygenase, kynurenine, quinolinic acid, and melatonin, may improve immunity in an organism and induce anti-inflammatory responses. The immune tolerance processes mediated by tryptophan metabolites are not well understood. Recent studies have reported that the enzymes that break down tryptophan through the kynurenine metabolic pathway are found in numerous cell types, including immunocytes. Moreover, some tryptophan metabolites have been shown to play a role in the inhibition of T lymphocyte proliferation, elevation of immunoglobulin levels in the blood, and promotion of antigen-presenting organization in tissues. This review summarizes the effects and mechanisms of tryptophan and metabolites in immune functions in livestock and poultry. It also highlights the areas in which our understanding of the role(s) of tryptophan is incomplete and suggests possible future research that might prove of benefit to livestock and poultry producers.
[Mh] Termos MeSH primário: Suplementos Nutricionais
Imunomodulação/efeitos dos fármacos
Indolamina-Pirrol 2,3,-Dioxigenase/imunologia
Linfócitos/efeitos dos fármacos
Triptofano/imunologia
[Mh] Termos MeSH secundário: Ração Animal
Animais
Seres Humanos
Imunidade Inata
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
Cinurenina/imunologia
Cinurenina/metabolismo
Gado
Linfócitos/citologia
Linfócitos/imunologia
Melatonina/imunologia
Melatonina/metabolismo
Aves Domésticas/imunologia
Ácido Quinolínico/imunologia
Ácido Quinolínico/metabolismo
Serotonina/imunologia
Serotonina/metabolismo
Suínos/imunologia
Triptofano/administração & dosagem
Triptofano/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 333DO1RDJY (Serotonin); 343-65-7 (Kynurenine); 8DUH1N11BX (Tryptophan); F6F0HK1URN (Quinolinic Acid); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1007/s00726-016-2351-8


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[PMID]:28460761
[Au] Autor:Samarghandian S; Azimi-Nezhad M; Farkhondeh T
[Ad] Endereço:Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran. Electronic address: samarghandians@mums.ac.ir.
[Ti] Título:Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats.
[So] Source:Indian Heart J;69(2):151-159, 2017 Mar - Apr.
[Is] ISSN:0019-4832
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Crocus sativus L. (saffron) has many biological effects such as antioxidant property. The present study investigated the immunomodulatory effects of the aqueous saffron extract on streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: In this study, the rats were divided into the following groups of 9 animals each: control, untreated diabetic, three saffron extract-treated diabetic groups. Diabetes was induced by STZ in rats. Saffron was administered 3 days after STZ administration; these injections were continued to the end of the study (4 weeks). At the end of the 4-week period, blood was drawn for biochemical assays and the abdominal aorta was removed for detecting the inflammatory cytokines expression. RESULTS: We found that saffron decreased blood glucose, malondialdehyde, nitric oxide, total lipids, triglycerides, cholesterol levels significantly (p<0.01) and increased glutathione level, catalase, and superoxide dismutase activities in the saffron-treated diabetic groups compared with the untreated groups, in a dose dependent manner (p<0.05, p<0.01, p<0.001). On the other hand, saffron-treated diabetic rats inhibited the expression of inflammatory cytokines in the abdominal aorta versus the untreated diabetic rats. CONCLUSION: Our results validate the use of saffron as a treatment against diabetes mellitus and its vascular complications.
[Mh] Termos MeSH primário: Antioxidantes/uso terapêutico
Crocus
Diabetes Mellitus Experimental/tratamento farmacológico
Imunomodulação
Lipídeos/sangue
Oxidantes/sangue
Estresse Oxidativo/efeitos dos fármacos
Extratos Vegetais/uso terapêutico
Espécies Reativas de Oxigênio/sangue
[Mh] Termos MeSH secundário: Animais
Glicemia/metabolismo
Diabetes Mellitus Experimental/sangue
Diabetes Mellitus Experimental/imunologia
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Blood Glucose); 0 (Lipids); 0 (Oxidants); 0 (Plant Extracts); 0 (Reactive Oxygen Species)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29363966
[Au] Autor:Van den Abbeele P; Taminiau B; Pinheiro I; Duysburgh C; Jacobs H; Pijls L; Marzorati M
[Ad] Endereço:ProDigest bvba , Technologiepark 3, 9052 Ghent, Belgium.
[Ti] Título:Arabinoxylo-Oligosaccharides and Inulin Impact Inter-Individual Variation on Microbial Metabolism and Composition, Which Immunomodulates Human Cells.
[So] Source:J Agric Food Chem;66(5):1121-1130, 2018 Feb 07.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fecal batch fermentations coupled to cocultures of epithelial cells and macrophages were used to compare how arabinoxylo-oligosaccharides (AXOS) and inulin modulate gut microbial activity and composition of three different human donors and subsequently the epithelial permeability and immune response. Both inulin and AXOS decreased the pH during incubation (-1.5 pH units), leading to increased productions of acetate, propionate, and butyrate. Differences in terms of metabolites production could be linked to specific microbial alterations at genus level upon inulin/AXOS supplementation (i.e., Bifidobacterium, Bacteroides, Prevotella and unclassified Erysipelotrichaceae), as shown by 16S-targeted Illumina sequencing. Both products stimulated gut barrier and immune function with increases in TEER, NF-KB, IL-10, and IL-6. Ingredients with different structures selectively modulate the microbiota of a specific donor leading to differential changes at metabolic level. The extent of this effect is donor specific and is linked to a final specific modulation of the host's immune system.
[Mh] Termos MeSH primário: Microbioma Gastrointestinal/efeitos dos fármacos
Imunomodulação/efeitos dos fármacos
Inulina/farmacologia
Oligossacarídeos/farmacologia
Xilanos/farmacologia
[Mh] Termos MeSH secundário: Acetatos/metabolismo
Butiratos/metabolismo
Células CACO-2
Fezes/microbiologia
Fermentação
Microbioma Gastrointestinal/imunologia
Microbioma Gastrointestinal/fisiologia
Seres Humanos
Concentração de Íons de Hidrogênio
Propionatos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Butyrates); 0 (Oligosaccharides); 0 (Propionates); 0 (Xylans); 9005-80-5 (Inulin); 9040-27-1 (arabinoxylan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b04611


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[PMID]:28747344
[Au] Autor:Burbage M; Keppler SJ; Montaner B; Mattila PK; Batista FD
[Ad] Endereço:Lymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, United Kingdom.
[Ti] Título:The Small Rho GTPase TC10 Modulates B Cell Immune Responses.
[So] Source:J Immunol;199(5):1682-1695, 2017 09 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rho family GTPases regulate diverse cellular events, such as cell motility, polarity, and vesicle traffic. Although a wealth of data exists on the canonical Rho GTPases RhoA, Rac1, and Cdc42, several other family members remain poorly studied. In B cells, we recently demonstrated a critical role for Cdc42 in plasma cell differentiation. In this study, we focus on a close homolog of Cdc42, TC10 (also known as RhoQ), and investigate its physiological role in B cells. By generating a TC10-deficient mouse model, we show that despite reduced total B cell numbers, B cell development in these mice occurs normally through distinct developmental stages. Upon immunization, IgM levels were reduced and, upon viral infection, germinal center responses were defective in TC10-deficient mice. BCR signaling was mildly affected, whereas cell migration remained normal in TC10-deficient B cells. Furthermore, by generating a TC10/Cdc42 double knockout mouse model, we found that TC10 can compensate for the lack of Cdc42 in TLR-induced cell activation and proliferation, so the two proteins play partly redundant roles. Taken together, by combining in vivo and in vitro analysis using TC10-deficient mice, we define the poorly studied Rho GTPase TC10 as an immunomodulatory molecule playing a role in physiological B cell responses.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Infecções por Orthomyxoviridae/imunologia
Vaccinia/imunologia
Proteína cdc42 de Ligação ao GTP/metabolismo
Proteínas rho de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Proliferação Celular
Células Cultivadas
Centro Germinativo/imunologia
Imunomodulação
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Receptores de Antígenos de Linfócitos B/metabolismo
Transdução de Sinais
Proteína cdc42 de Ligação ao GTP/genética
Proteínas rho de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cdc42 protein, mouse); 0 (Receptors, Antigen, B-Cell); EC 3.6.1.- (Rhoq protein, mouse); EC 3.6.5.2 (cdc42 GTP-Binding Protein); EC 3.6.5.2 (rho GTP-Binding Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1602167


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[PMID]:28449719
[Au] Autor:Bongard N; Lapuente D; Windmann S; Dittmer U; Tenbusch M; Bayer W
[Ad] Endereço:Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
[Ti] Título:Interference of retroviral envelope with vaccine-induced CD8 T cell responses is relieved by co-administration of cytokine-encoding vectors.
[So] Source:Retrovirology;14(1):28, 2017 Apr 27.
[Is] ISSN:1742-4690
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Retroviral envelope (Env) proteins are known to exhibit immunosuppressive properties, which become apparent not only in retroviral infections, but also in gene-based immunizations using retroviral immunogens, where envelope interferes with the induction of CD8 T cell responses towards another, simultaneously or subsequently delivered, immunogen. RESULTS: In the Friend retrovirus mouse model, immunization with a plasmid encoding the Friend murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a strong GagL -specific CD8 T cell response, while the response was completely abrogated by co-immunization with an F-MuLV Env-encoding plasmid. In order to overcome this interference of retroviral envelope, we employed plasmids encoding the cytokines interleukin (IL) 1ß, IL2, IL12, IL15, IL21, IL28A or granulocyte-macrophage colony-stimulating factor (GM-CSF) as genetic adjuvants. Co-application of plasmids encoding IL2, IL12, IL21, IL28A and especially GM-CSF rescued the induction of GagL -specific CD8 T cells in mice vaccinated with FV Leader-Gag and Env. Mice that were immunized with plasmids encoding Leader-Gag and Env and the cytokines IL1ß, IL12, IL15, IL28A or GM-CSF, but not Leader-Gag and Env without any cytokine, showed significantly reduced viral loads upon a high-dose Friend virus challenge infection. CONCLUSIONS: Our data demonstrate the potency of cytokine-encoding vectors as adjuvants and immune modulators in composite vaccines for anti-retroviral immunization.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Citocinas/genética
Vírus da Leucemia Murina de Friend/imunologia
Vacinas de DNA/imunologia
Proteínas do Envelope Viral/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos
Animais
Citocinas/imunologia
Feminino
Vírus da Leucemia Murina de Friend/genética
Produtos do Gene gag/genética
Produtos do Gene gag/imunologia
Vetores Genéticos
Imunização
Imunomodulação
Interleucina-15/genética
Interleucina-15/imunologia
Interleucina-2/genética
Interleucina-2/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Plasmídeos
Infecções por Retroviridae/imunologia
Vacinas de DNA/administração & dosagem
Proteínas do Envelope Viral/genética
Proteínas do Envelope Viral/metabolismo
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Cytokines); 0 (Gene Products, gag); 0 (Interleukin-15); 0 (Interleukin-2); 0 (Vaccines, DNA); 0 (Viral Envelope Proteins); 0 (Viral Vaccines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s12977-017-0352-7



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