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[PMID]:28888053
[Au] Autor:Guo H; Zhao N; Gao H; He X
[Ad] Endereço:Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
[Ti] Título:Mesenchymal Stem Cells Overexpressing Interleukin-35 Propagate Immunosuppressive Effects in Mice.
[So] Source:Scand J Immunol;86(5):389-395, 2017 Nov.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To explore generation of interleukin (IL)-35-expressing mouse adipocyte-derived mesenchymal stem cells (Ad-MSCs) using lentiviral vector and their potential immunosuppressive effects in mice. Ad-MSCs were isolated and cultured in vitro and transfected with a lentivirus vector for overexpression of the therapeutic murine IL-35 gene. IL-35 expression in transfected MSCs (IL-35-MSCs) was quantified by enzyme-linked immunosorbent assay (ELISA). The lymphocytes subsets after one-way mixed lymphocyte culture and in vivo intravenous transplantation were analysed by flow cytometry to evaluate the immunosuppressive effects of IL-35-MSCs. ELISA was performed to examine IL-10, IL-17A and IL-35 expression in lymphocyte culture. Mouse Ad-MSCs were isolated and cultured. IL-35 was expressed in the MSC supernatant and serum after IL-35 transduction into Ad-MSCs by lentiviral vector transfection in vitro and in vivo. The percentage of CD4 CD25 T regulatory (Treg) cells in mice treated with IL-35-MSCs significantly increased. IL-35-MSCs upregulated the CD4 CD25 Treg cells in the allogeneic mixed lymphocyte reaction system, and lowered the percentage of CD4 T cells compared with the other two control groups (P < 0.01). IL-17A expression significantly decreased and IL-10 expression significantly increased in IL-35-MSCs and MSCs when compared by ELISA to the control groups (P < 0.01). IL-35-transduced Ad-MSCs in vivo can enhance proliferation of CD4 CD25 Treg cells and suppress the function of effector T cells such as T helper (Th) 1, Th2 and Th17 cells and may reduce the development of allograft rejection. Our data suggest that transduced Ad-MSCs overexpressing IL-35 may provide a useful approach for basic research on cell-based immunotolerance therapy for inducing transplantation tolerance.
[Mh] Termos MeSH primário: Tolerância Imunológica
Interleucinas/metabolismo
Células Mesenquimais Estromais/imunologia
[Mh] Termos MeSH secundário: Adipócitos/citologia
Adipócitos/imunologia
Animais
Células Cultivadas
Interleucinas/genética
Teste de Cultura Mista de Linfócitos
Masculino
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/citologia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Linfócitos T Auxiliares-Indutores/imunologia
Linfócitos T Reguladores/imunologia
Transfecção
Tolerância ao Transplante
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukins); 0 (Recombinant Proteins); 0 (interleukin-35, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12613


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[PMID]:28768873
[Au] Autor:Rappocciolo G; Jais M; Piazza PA; DeLucia DC; Jenkins FJ; Rinaldo CR
[Ad] Endereço:Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA giovanna@pitt.edu.
[Ti] Título:Human Herpesvirus 8 Infects and Replicates in Langerhans Cells and Interstitial Dermal Dendritic Cells and Impairs Their Function.
[So] Source:J Virol;91(20), 2017 Oct 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The predominant types of dendritic cells (DC) in the skin and mucosa are Langerhans cells (LC) and interstitial dermal DC (iDDC). LC and iDDC process cutaneous antigens and migrate out of the skin and mucosa to the draining lymph nodes to present antigens to T and B cells. Because of the strategic location of LC and iDDC and the ability of these cells to capture and process pathogens, we hypothesized that they could be infected with human herpesvirus 8 (HHV-8) (Kaposi's sarcoma [KS]-associated herpesvirus) and have an important role in the development of KS. We have previously shown that HHV-8 enters monocyte-derived dendritic cells (MDDC) through DC-SIGN, resulting in nonproductive infection. Here we show that LC and iDDC generated from pluripotent cord blood CD34 cell precursors support productive infection with HHV-8. Anti-DC-SIGN monoclonal antibody (MAb) inhibited HHV-8 infection of iDDC, as shown by low expression levels of viral proteins and DNA. In contrast, blocking of both langerin and the receptor protein tyrosine kinase ephrin A2 was required to inhibit HHV-8 infection of LC. Infection with HHV-8 did not alter the cell surface expression of langerin on LC but downregulated the expression of DC-SIGN on iDDC, as we previously reported for MDDC. HHV-8-infected LC and iDDC had a reduced ability to stimulate allogeneic CD4 T cells in the mixed-lymphocyte reaction. These results indicate that HHV-8 can target both LC and iDDC for productive infection via different receptors and alter their function, supporting their potential role in HHV-8 pathogenesis and KS. Here we show that HHV-8, a DNA tumor virus that causes Kaposi's sarcoma, infects three types of dendritic cells: monocyte-derived dendritic cells, Langerhans cells, and interstitial dermal dendritic cells. We show that different receptors are used by this virus to infect these cells. DC-SIGN is a major receptor for infection of both monocyte-derived dendritic cells and interstitial dermal dendritic cells, yet the virus fully replicates only in the latter. HHV-8 uses langerin and the ephrin A2 receptor to infect Langerhans cells, which support full HHV-8 lytic replication. This infection of Langerhans cells and interstitial dermal dendritic cells results in an impaired ability to stimulate CD4 helper T cell responses. Taken together, our data show that HHV-8 utilizes alternate receptors to differentially infect and replicate in these tissue-resident DC and support the hypothesis that these cells play an important role in HHV-8 infection and pathogenesis.
[Mh] Termos MeSH primário: Células Dendríticas/virologia
Herpesvirus Humano 8/fisiologia
Células de Langerhans/virologia
[Mh] Termos MeSH secundário: Antígenos CD/metabolismo
Moléculas de Adesão Celular/imunologia
Moléculas de Adesão Celular/metabolismo
Diferenciação Celular
Células Cultivadas
Células Dendríticas/imunologia
Efrina-A2/antagonistas & inibidores
Herpesvirus Humano 8/genética
Herpesvirus Humano 8/imunologia
Herpesvirus Humano 8/patogenicidade
Seres Humanos
Células de Langerhans/imunologia
Células de Langerhans/patologia
Lectinas Tipo C/antagonistas & inibidores
Lectinas Tipo C/imunologia
Lectinas Tipo C/metabolismo
Teste de Cultura Mista de Linfócitos
Lectinas de Ligação a Manose/antagonistas & inibidores
Lectinas de Ligação a Manose/metabolismo
Receptores de Superfície Celular/imunologia
Receptores de Superfície Celular/metabolismo
Sarcoma de Kaposi/virologia
Pele/citologia
Pele/imunologia
Pele/virologia
Linfócitos T Auxiliares-Indutores/imunologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD207 protein, human); 0 (Cell Adhesion Molecules); 0 (DC-specific ICAM-3 grabbing nonintegrin); 0 (Ephrin-A2); 0 (Lectins, C-Type); 0 (Mannose-Binding Lectins); 0 (Receptors, Cell Surface)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE


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[PMID]:28582644
[Au] Autor:Mundt S; Basler M; Sawitzki B; Groettrup M
[Ad] Endereço:Division of Immunology, Department of Biology, Universitaetsstrasse 10, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany. Electronic address: mundt@immunology.uzh.ch.
[Ti] Título:No prolongation of skin allograft survival by immunoproteasome inhibition in mice.
[So] Source:Mol Immunol;88:32-37, 2017 Aug.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The immunoproteasome, a distinct class of proteasomes, which is inducible under inflammatory conditions and constitutively expressed in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. Moreover, inhibition of the immunoproteasome subunit LMP7 ameliorates clinical symptoms of autoimmune diseases in vivo and was shown to suppress the development of T helper cell (Th) 1 and Th17 cells and to promote regulatory T-cell (Treg) generation independently of its function in antigen processing. Since Th1 and Th17 cells are detrimental and Treg cells are critical for transplant acceptance, we investigated the influence of the LMP7-selective inhibitor ONX 0914 in a mixed lymphocyte reaction (MLR) in vitro as well as on allograft rejection in a MHC-disparate (C57BL/6 to BALB/c) and a multiple minor histocompatibility antigen (miHA)-disparate (B10.Br to C3H) model of skin transplantation in vivo. Although we observed reduced allo-specific IL-17 production of T cells in vitro, we found that selective inhibition of LMP7 had neither an influence on allograft survival in an MHC-mismatch model nor in a multiple minor mismatch skin transplantation model. We conclude that inhibition of the immunoproteasome is not effective in prolonging skin allograft survival in skin allotransplantation.
[Mh] Termos MeSH primário: Sobrevivência de Enxerto/imunologia
Complexo de Endopeptidases do Proteassoma/metabolismo
Inibidores de Proteassoma/farmacologia
Transplante de Pele/métodos
Pele/imunologia
[Mh] Termos MeSH secundário: Aloenxertos
Animais
Doenças Autoimunes/imunologia
Doenças Autoimunes/patologia
Bortezomib/farmacologia
Rejeição de Enxerto/imunologia
Interleucina-17/imunologia
Teste de Cultura Mista de Linfócitos
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C3H
Camundongos Endogâmicos C57BL
Oligopeptídeos/farmacologia
Complexo de Endopeptidases do Proteassoma/imunologia
Pele/citologia
Linfócitos T Reguladores/imunologia
Células Th1/imunologia
Células Th17/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-17); 0 (Oligopeptides); 0 (PR-957); 0 (Proteasome Inhibitors); 69G8BD63PP (Bortezomib); EC 3.4.25.1 (LMP7 protein); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE


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[PMID]:28400539
[Au] Autor:Roussel M; Ferrell PB; Greenplate AR; Lhomme F; Le Gallou S; Diggins KE; Johnson DB; Irish JM
[Ad] Endereço:Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; mikael.roussel@chu-rennes.fr.
[Ti] Título:Mass cytometry deep phenotyping of human mononuclear phagocytes and myeloid-derived suppressor cells from human blood and bone marrow.
[So] Source:J Leukoc Biol;102(2):437-447, 2017 Aug.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274. MPS diversity was characterized for 1) circulating monocytes from healthy donors, 2) monocyte-derived macrophages further polarized in vitro (i.e., M-CSF, GM-CSF, IL-4, IL-10, IFN-γ, or LPS long-term stimulations), 3) monocyte-derived DCs, and 4) myeloid-derived suppressor cells (MDSCs), generated in vitro from bone marrow and/or peripheral blood. Known monocyte subsets were detected in peripheral blood to validate the panel and analysis pipeline. Then, using various culture conditions and stimuli before CyTOF analysis, we constructed a multidimensional framework for the MPS compartment, which was registered against historical M1 or M2 macrophages, monocyte subsets, and DCs. Notably, MDSCs generated in vitro from bone marrow expressed more S100A9 than when generated from peripheral blood. Finally, to test the approach in vivo, peripheral blood from patients with melanoma ( = 5) was characterized and observed to be enriched for MDSCs with a phenotype of CD14 HLA-DR S100A9 (3% of PBMCs in healthy donors, 15.5% in patients with melanoma, < 0.02). In summary, mass cytometry comprehensively characterized phenotypes of human monocyte, MDSC, macrophage, and DC subpopulations in both in vitro models and patients.
[Mh] Termos MeSH primário: Células Dendríticas/citologia
Citometria de Fluxo/métodos
Macrófagos/citologia
Monócitos/citologia
Células Supressoras Mieloides/citologia
[Mh] Termos MeSH secundário: Seres Humanos
Teste de Cultura Mista de Linfócitos
Fagócitos
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.5MA1116-457R


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[PMID]:28219888
[Au] Autor:Zhou Y; Chen H; Liu L; Yu X; Sukhova GK; Yang M; Zhang L; Kyttaris VC; Tsokos GC; Stillman IE; Ichimura T; Bonventre JV; Libby P; Shi GP
[Ad] Endereço:Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
[Ti] Título:CD74 Deficiency Mitigates Systemic Lupus Erythematosus-like Autoimmunity and Pathological Findings in Mice.
[So] Source:J Immunol;198(7):2568-2577, 2017 Apr 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro. The presence of kidney TECs from mice, rather than from wild-type mice, produced significantly stronger histones, dsDNA, and ribonucleoprotein-Smith Ag complex-induced CD4 T cell activation. Splenocytes from CD74-deficient mice had muted responses in a MLR and to the autoantigen histones. Compared with mice, mice had reduced kidney and spleen sizes, splenic activated T cells and B cells, serum IgG and autoantibodies, urine albumin/creatinine ratio, kidney Periodic acid-Schiff score, IgG and C3 deposition, and serum IL-6 and IL-17A levels, but serum IL-2 and TGF-ß levels were increased. Study of chronic graft-versus-host C57BL/6 mice that received donor splenocytes from B6.C- /KhEg mice and those that received syngeneic donor splenocytes yielded similar observations. CD74 deficiency reduced lupus-like autoimmunity and kidney pathology in chronic graft-versus-host mice. This investigation establishes the direct participation of CD74 in autoimmunity and highlights a potential role for CD74 in kidney TECs, together with professional APCs in systemic lupus erythematosus.
[Mh] Termos MeSH primário: Células Apresentadoras de Antígenos/imunologia
Antígenos de Diferenciação de Linfócitos B/imunologia
Doenças Autoimunes/imunologia
Autoimunidade/imunologia
Células Epiteliais/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
[Mh] Termos MeSH secundário: Animais
Apresentação do Antígeno/imunologia
Western Blotting
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Doença Enxerto-Hospedeiro/imunologia
Imuno-Histoquímica
Túbulos Renais/imunologia
Nefrite Lúpica/imunologia
Ativação Linfocitária/imunologia
Teste de Cultura Mista de Linfócitos
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Differentiation, B-Lymphocyte); 0 (Histocompatibility Antigens Class II); 0 (invariant chain)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1600028


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[PMID]:28152014
[Au] Autor:Nelson N; Szekeres K; Iclozan C; Rivera IO; McGill A; Johnson G; Nwogu O; Ghansah T
[Ad] Endereço:Department of Molecular Medicine, University of South Florida, Tampa, Florida, United States of America.
[Ti] Título:Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer.
[So] Source:PLoS One;12(2):e0170197, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model. We also showed that this loss of Ikaros expression is associated with a significant decrease in CD4+ and CD8+ T cell percentages but increased CD4+CD25+ Tregs in TB mice. In this study, we evaluated the effects of the dietary flavonoid apigenin (API), on Ikaros expression and T cell immune responses. Treatment of splenocytes from naïve mice with (API) stabilized Ikaros expression and prevented Ikaros downregulation in the presence of murine Panc02 cells in vitro, similar to the proteasome inhibitor MG132. In vivo treatment of TB mice with apigenin (TB-API) improved survival, reduced tumor weights and prevented splenomegaly. API treatment also restored protein expression of some Ikaros isoforms, which may be attributed to its moderate inhibition of CK2 activity from splenocytes of TB-API mice. This partial restoration of Ikaros expression was accompanied by a significant increase in CD4+ and CD8+ T cell percentages and a reduction in Treg percentages in TB-API mice. In addition, CD8+ T cells from TB-API mice produced more IFN-γ and their splenocytes were better able to prime allogeneic CD8+ T cell responses compared to TB mice. These results provide further evidence that Ikaros is regulated by CK2 in our pancreatic cancer model. More importantly, our findings suggest that API may be a possible therapeutic agent for stabilizing Ikaros expression and function to maintain T cell homeostasis in murine PC.
[Mh] Termos MeSH primário: Apigenina/uso terapêutico
Caseína Quinase II/antagonistas & inibidores
Fator de Transcrição Ikaros/metabolismo
Neoplasias Pancreáticas/tratamento farmacológico
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Regulação para Baixo/efeitos dos fármacos
Feminino
Homeostase/efeitos dos fármacos
Leupeptinas/uso terapêutico
Teste de Cultura Mista de Linfócitos
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Neoplasias Pancreáticas/imunologia
Neoplasias Pancreáticas/metabolismo
Inibidores de Proteassoma/uso terapêutico
Proteína Fosfatase 1/metabolismo
Linfócitos T/imunologia
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Leupeptins); 0 (Proteasome Inhibitors); 0 (Tumor Suppressor Proteins); 0 (Zfpn1a1 protein, mouse); 148971-36-2 (Ikaros Transcription Factor); 7V515PI7F6 (Apigenin); EC 2.7.11.1 (Casein Kinase II); EC 3.1.3.16 (Protein Phosphatase 1); RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170916
[Lr] Data última revisão:
170916
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170197


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[PMID]:28092865
[Au] Autor:Iwaszkiewicz-Grzes D; Cholewinski G; Kot-Wasik A; Trzonkowski P; Dzierzbicka K
[Ad] Endereço:Department of Organic Chemistry, Gdansk University of Technology, ul. G. Narutowicza 11/12, 80-233 Gdansk, Poland; Department of Clinical Immunology and Transplantology, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland.
[Ti] Título:Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cells.
[So] Source:Int Immunopharmacol;44:137-142, 2017 Mar.
[Is] ISSN:1878-1705
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors. It was confirmed in the mixed leucocyte reaction (MLR), in which T cells challenged with DCs pretreated with the analogs showed decreased proliferation and reduced cytokine secretion. The most interesting activity in this series of studies, that is, the suppression of CD86 receptor expression, decreased cytokine production and suppressed mixed leucocyte reaction, exhibited (mycophenoyl-N-3-propyl)-9-acridone-4-carboxamide ester 5a and (mycophenoyl-N-5-pentyl)-9-acridone-4-carboxamide ester 5b. These compounds reduced also the secretion of IL-2 and IL-15. In addition, they increased secretion of suppressive IL-10. Equally promising results were obtained for the N-mycophenoyl-D-glutamic acid 4b, which previously gave the highest value of selectivity. Acridone derivatives of MPA are therefore good immunosuppressive drug candidates for further testing.
[Mh] Termos MeSH primário: Doenças Autoimunes/tratamento farmacológico
Células Dendríticas/efeitos dos fármacos
Rejeição de Enxerto/tratamento farmacológico
Imunossupressores/farmacologia
Ácido Micofenólico/farmacologia
Transplante de Órgãos
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Acridonas/química
Antígeno B7-2/genética
Antígeno B7-2/metabolismo
Diferenciação Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Células Dendríticas/imunologia
Seres Humanos
Interleucina-10/metabolismo
Interleucina-2/metabolismo
Ativação Linfocitária/efeitos dos fármacos
Teste de Cultura Mista de Linfócitos
Ácido Micofenólico/análogos & derivados
Ácido Micofenólico/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridones); 0 (B7-2 Antigen); 0 (IL10 protein, human); 0 (Immunosuppressive Agents); 0 (Interleukin-2); 130068-27-8 (Interleukin-10); HU9DX48N0T (Mycophenolic Acid)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE


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[PMID]:27923881
[Au] Autor:Zhang Y; Yu S; Li X; Yang B; Wu C
[Ad] Endereço:Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology; Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
[Ti] Título:The ligands of translocator protein inhibit human Th1 responses and the rejection of murine skin allografts.
[So] Source:Clin Sci (Lond);131(4):297-308, 2017 Feb 01.
[Is] ISSN:1470-8736
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The translocator protein (TSPO) ligands affected inflammatory and immune responses. However, the exact effects of TSPO ligands on Th1 responses in vitro and in vivo are still unclear. In the present study, we found that TSPO ligands, FGIN1-27 and Ro5-4864, suppressed the cytokine production in a dose-dependent manner by purified human CD4 T-cells from peripheral blood mononuclear cells (PBMCs) after stimulation. TSPO ligands inhibited the production of interferon γ (IFN-γ) by memory CD4 T-cells and the differentiation of naïve CD4 T-cells into Th1 cells via suppressing the activity of the corresponding transcription factors as indicated by reduced expression of T-bet and down-regulation of STAT1, STAT4 and STAT5 phosphorylation. TSPO ligands suppressed cell proliferation and activation of CD4 T-cells by the inhibition of TCR signal transduction including membrane proteins: Zap, Lck, Src; cytoplasm proteins: Plcγ1, Slp-76, ERK, JNK and the nucleoproteins: c-Jun and c-Fos. In addition, FGIN1-27 inhibited mixed lymphocyte reactions by human or murine cells. After the transplantation of allogeneic murine skin, injection of FGIN1-27 into mice prevented graft rejection by inhibition of cell infiltration and IFN-γ production. Taken together, our data suggest that TSPO ligands inhibit Th1 cell responses and might be novel therapeutic medicine for the treatment of autoimmune diseases and prevention of transplant rejection.
[Mh] Termos MeSH primário: Rejeição de Enxerto/prevenção & controle
Ácidos Indolacéticos/uso terapêutico
Transplante de Pele
Células Th1/imunologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
Benzodiazepinonas/imunologia
Linfócitos T CD4-Positivos/imunologia
Células Cultivadas
Citocinas/biossíntese
Avaliação Pré-Clínica de Medicamentos/métodos
Feminino
Rejeição de Enxerto/imunologia
Seres Humanos
Ácidos Indolacéticos/imunologia
Ligantes
Ativação Linfocitária/imunologia
Teste de Cultura Mista de Linfócitos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Fosforilação/imunologia
Receptores de GABA/metabolismo
Fatores de Transcrição STAT/metabolismo
Transdução de Sinais/imunologia
Proteínas com Domínio T-Box/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzodiazepinones); 0 (Bzrp protein, mouse); 0 (Cytokines); 0 (Indoleacetic Acids); 0 (Ligands); 0 (Receptors, GABA); 0 (STAT Transcription Factors); 0 (T-Box Domain Proteins); 0 (T-box transcription factor TBX21); 0 (TSPO protein, human); 142720-24-9 (N,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide); 2QW0IK1742 (4'-chlorodiazepam)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161208
[St] Status:MEDLINE
[do] DOI:10.1042/CS20160547


  9 / 11298 MEDLINE  
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[PMID]:27856191
[Au] Autor:Davis RJ; Silvin C; Allen CT
[Ad] Endereço:Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States.
[Ti] Título:Avoiding phagocytosis-related artifact in myeloid derived suppressor cell T-lymphocyte suppression assays.
[So] Source:J Immunol Methods;440:12-18, 2017 Jan.
[Is] ISSN:1872-7905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Myeloid-derived suppressor cells (MDSCs) have garnered much attention in recent years as a potential target for altering the immunosuppressive tumor microenvironment in a variety of solid tumor types. The ability to accurately assess the immunosuppressive capacity of MDSCs is fundamental to the development of therapeutic approaches aimed at disabling these immunosuppressive functions. In this article we provide evidence that the use of CD3/28 coated microbeads leads to artefactual T-lymphocyte suppression due to sequestration of beads by MDSCs isolated from the spleens of wild-type mice bearing subcutaneous syngeneic, carcinogen-induced oral cavity carcinomas. Mechanisms of this finding may include early MDSC death and acquisition of phagocytic capacity. These artefactual findings were avoided by eliminating the use of microbeads and instead using plate bound CD3/28 antibody as the T-lymphocyte stimulus. We propose model-specific validation of microbead-based MDSC assays, or use of an alternative stimulation approach such as plate bound CD3/28 antibodies.
[Mh] Termos MeSH primário: Ativação Linfocitária
Teste de Cultura Mista de Linfócitos/métodos
Neoplasias Bucais/imunologia
Células Supressoras Mieloides/imunologia
Fagocitose
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Artefatos
Antígenos CD28/imunologia
Antígenos CD28/metabolismo
Complexo CD3/imunologia
Complexo CD3/metabolismo
Morte Celular
Proliferação Celular
Células Cultivadas
Técnicas de Cocultura
Citometria de Fluxo
Camundongos Endogâmicos C57BL
Neoplasias Bucais/metabolismo
Neoplasias Bucais/patologia
Células Supressoras Mieloides/metabolismo
Células Supressoras Mieloides/patologia
Reprodutibilidade dos Testes
Linfócitos T/metabolismo
Linfócitos T/patologia
Fatores de Tempo
Evasão Tumoral
Microambiente Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD28 Antigens); 0 (CD3 Complex)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE


  10 / 11298 MEDLINE  
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[PMID]:27820781
[Au] Autor:Dupin C; Lhuillier E; Létuvé S; Pretolani M; Thabut G; Mal H; Carosella E; Schilte C; Mordant P; Castier Y; Bunel V; Danel C; Rouas-Freiss N; Brugière O
[Ad] Endereço:1 INSERM UMR1152, Paris Diderot University, Paris, France. 2 CEA, IMETI, Hemato-immunology research department, Saint-Louis Hospital, Paris, France. 3 Paris Diderot University, Sorbonne Paris Cité, IUH, Paris, France. 4 Pneumology B and Lung Transplantation Department, Bichat Hospital, Paris, France. 5 Laboratory of Excellence INFLAMEX, Université Sorbonne Paris-Cité, Paris, France. 6 Département Hospitalo-Universitaire FIRE, Paris, France. 7 Pathology Department, Bichat hospital, Paris, France. 8 Thoracic Surgery Department, Bichat hospital, Paris, France. 9 Anesthesia Intensive Care, Bichat Hospital, Paris, France.
[Ti] Título:Inhibition of T Cell Alloreactivity by Bronchial Epithelium Is Impaired in Lung Transplant Recipients, Through Pathways Involving TGF-ß, IL-10 and HLA-G.
[So] Source:Transplantation;101(9):2192-2199, 2017 Sep.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx) results from bronchial epithelial cell (BECs) damages, thought to be orchestrated by T cells primed by antigen-presenting cell presenting alloantigens. In this cell cross-talk, BECs are also suspected to play a pivotal immunosuppressive role in T cell alloreactivity. We studied the immunomodulating role of BECs in a human ex vivo model of allogeneic T cell response, both in healthy subjects and LTx recipients. METHODS: BECs from 35 LTx recipients (n = 22 stable, n = 13 BOS) and healthy controls (n = 25) were cultured as primary cell cultures. Their inhibitory capacities through the involvement of tolerogenic molecules (HLA-G, TGF-ß, and IL-10) were tested on a mixed lymphocyte reaction between antigen-presenting cells and recipient T cells. RESULTS: Control BECs inhibited T cell alloproliferation by a mean of 53 ± 7%. This inhibitory effect of BECs was significantly reduced in the stable LTx group (24 ± 8%, P = 0.009), but not in the BOS TxP group (53 ± 10%, P = 0.97). Neutralization of HLA-G, TGF-ß, and IL-10 partially restored T cell alloproliferation, arguing for their involvement in the immunosuppressive effect of BECs. BECs culture supernatant from stable LTx patients with impaired BEC properties showed a skewed Th2-type secretion profile (high IL-4/IFN-γ ratio). CONCLUSIONS: The inhibitory properties of BECs are dysregulated in stable LTx recipients, which could suggest their instrumental role in the initiation of BOS process and potential targeted therapies.
[Mh] Termos MeSH primário: Bronquiolite Obliterante/etiologia
Células Epiteliais/metabolismo
Antígenos HLA-G/metabolismo
Imunidade nas Mucosas
Interleucina-10/metabolismo
Transplante de Pulmão/efeitos adversos
Mucosa Respiratória/metabolismo
Linfócitos T/metabolismo
Fator de Crescimento Transformador beta/metabolismo
[Mh] Termos MeSH secundário: Bronquiolite Obliterante/imunologia
Bronquiolite Obliterante/metabolismo
Bronquiolite Obliterante/patologia
Estudos de Casos e Controles
Proliferação Celular
Células Cultivadas
Técnicas de Cocultura
Células Epiteliais/imunologia
Células Epiteliais/patologia
Feminino
Antígenos HLA-G/imunologia
Seres Humanos
Interleucina-10/imunologia
Ativação Linfocitária
Teste de Cultura Mista de Linfócitos
Masculino
Meia-Idade
Cultura Primária de Células
Estudos Prospectivos
Mucosa Respiratória/imunologia
Mucosa Respiratória/patologia
Transdução de Sinais
Linfócitos T/imunologia
Linfócitos T/patologia
Fator de Crescimento Transformador beta/imunologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA-G Antigens); 0 (IL10 protein, human); 0 (Transforming Growth Factor beta); 130068-27-8 (Interleukin-10)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001553



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