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[PMID]:29412476
[Au] Autor:Bakela K; Dimakopoulou M; Batsou P; Manidakis N; Athanassakis I
[Ad] Endereço:Laboratory of Immunology, Department of Biology, University of Crete, Heraklion, Crete, Greece.
[Ti] Título:Soluble MHC class II-driven therapy for a systemic lupus erythematosus murine experimental in vitro and in vivo model.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Taking into consideration the multiparametric nature of systemic lupus erythematosus (SLE), the severity and variability of symptoms and the lack of effective therapeutic approaches, this study took advantage of the recently described role of soluble major histocompatibility complex class II (sMHCII) molecules in maintaining tolerance to the organism and attempted to apply sMHCII proteins as a treatment to murine SLE experimental models in vitro as well as in vivo. After breaking tolerance to DNA in vitro, which was accompanied by development of specific anti-dsDNA antibodies, syngeneic or allogeneic sMHCII molecules, purified from healthy mouse serum, could significantly reduce the specific antibody levels and drive the system towards immunosuppression, as assessed by specific marker analysis on T cells and cytokine production by flow cytometry and ELISA, respectively. The in vivo experimental model consisted of pristane-induced SLE symptoms to BALB/c mice, which developed maximal levels of anti-dsDNA 2 months after pristane inoculation. Syngeneic or allogeneic sMHCII administration could alleviate pristane-induced symptoms, significantly decrease specific anti-dsDNA antibody production and develop immunosuppression to the host, as manifested by increase of CD4 + CTLA-4 +  and CD4 + CD25 +  cell populations in the spleen. Thus, the results presented in this study introduced the ability of sMHCII proteins to suppress specific autoantigen response, opening new areas of research and offering novel therapeutic approaches to SLE with expanding features to other autoimmune diseases.
[Mh] Termos MeSH primário: Anticorpos Antinucleares/imunologia
Autoantígenos/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
Tolerância Imunológica/imunologia
Imunoterapia/métodos
Lúpus Eritematoso Sistêmico/imunologia
Lúpus Eritematoso Sistêmico/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD4/metabolismo
Antígeno CTLA-4/metabolismo
Células Cultivadas
DNA/imunologia
Modelos Animais de Doenças
Imunossupressão
Subunidade alfa de Receptor de Interleucina-2/metabolismo
Lúpus Eritematoso Sistêmico/induzido quimicamente
Camundongos
Camundongos Endogâmicos BALB C
Baço/citologia
Baço/imunologia
Terpenos/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Antinuclear); 0 (Autoantigens); 0 (CD4 Antigens); 0 (CTLA-4 Antigen); 0 (Histocompatibility Antigens Class II); 0 (Il2ra protein, mouse); 0 (Interleukin-2 Receptor alpha Subunit); 0 (Terpenes); 26HZV48DT1 (pristane); 9007-49-2 (DNA)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12644


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[PMID]:29377903
[Au] Autor:Koldehoff M; Lindemann M; Ross SR; Elmaagacli AH
[Ad] Endereço:Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital of Essen, Essen, Germany.
[Ti] Título:Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line.
[So] Source:PLoS One;13(1):e0191482, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytomegalovirus (HCMV) reactivation is found frequently after allogeneic hematopoietic stem cell transplantation (alloSCT) and is associated with an increased treatment-related mortality. Recent reports suggest a link between HCMV and a reduced risk of cancer progression in patients with acute leukemia or lymphoma after alloSCT. Here we show that HCMV can inhibit the proliferation of the acute myeloid leukemia cell line Kasumi-1 and the promyeloid leukemia cell line NB4. HCMV induced a significant up-regulation of HLA-class-II-molecules, especially HLA-DR expression and an increase of apoptosis, granzyme B, perforin and IFN-γ secretion in Kasumi-1 cells cocultured with peripheral blood mononuclear cells (PBMCs). Indolamin-2,3-dioxygenase on the other hand led only to a significant dose-dependent effect on IFN-γ secretion without effects on proliferation. The addition of CpG-rich oligonucleotides and ganciclovir reversed those antiproliferative effects. We conclude that HCMV can enhance alloreactivity of PBMCs against Kasumi-1 and NB4 cells in vitro. To determine if this phenomenon may be clinically relevant further investigations will be required.
[Mh] Termos MeSH primário: Antígenos de Histocompatibilidade Classe II/imunologia
Leucemia Mieloide Aguda/imunologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Técnicas de Cocultura
Seres Humanos
Leucemia Mieloide Aguda/terapia
Leucemia Mieloide Aguda/virologia
Transplante de Células-Tronco
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Histocompatibility Antigens Class II)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191482


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[PMID]:28468970
[Au] Autor:Chowdhary VR; Krogman A; Tilahun AY; Alexander MP; David CS; Rajagopalan G
[Ad] Endereço:Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN 55905.
[Ti] Título:Concomitant Disruption of and Genes Facilitates the Development of Double Negative αß TCR Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen.
[So] Source:J Immunol;198(11):4413-4424, 2017 06 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mature peripheral double negative T (DNT) cells expressing αß TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated and genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors. Because HLA class II molecules present superantigens more efficiently than murine MHC class II molecules, CD4 CD8 double knockout (DKO) mice transgenically expressing HLA-DR3 or HLA-DQ8 molecules were generated. Although thymic cellularity was comparable between wild type (WT) and DKO mice, CD3 αß TCR thymocytes were significantly reduced in DKO mice, implying defects in thymic-positive selection. Splenic CD3 αß TCR cells and Foxp3 T regulatory cells were present in DKO mice but significantly reduced. However, the in vivo inflammatory responses and immunopathology elicited by acute challenge with the staphylococcal superantigen enterotoxin B were comparable between WT and DKO mice. Choric exposure to staphylococcal enterotoxin B precipitated a lupus-like inflammatory disease with characteristic lympho-monocytic infiltration in lungs, livers, and kidneys, along with production of anti-nuclear Abs in DKO mice as in WT mice. Overall, our results suggest that DNT cells can develop efficiently in vivo and chronic exposure to bacterial superantigens may precipitate a lupus-like autoimmune disease through activation of DNT cells.
[Mh] Termos MeSH primário: Antígenos CD4/genética
Antígenos CD4/imunologia
Antígenos CD8/genética
Antígenos CD8/imunologia
Enterotoxinas/imunologia
Superantígenos/imunologia
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos HLA-DQ/genética
Antígenos HLA-DQ/imunologia
Antígeno HLA-DR3/genética
Antígeno HLA-DR3/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Receptores de Antígenos de Linfócitos T alfa-beta/genética
Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
Baço/citologia
Baço/imunologia
Timo/citologia
Timo/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CD4 Antigens); 0 (CD8 Antigens); 0 (Enterotoxins); 0 (HLA-DQ Antigens); 0 (HLA-DQ8 antigen); 0 (HLA-DR3 Antigen); 0 (Histocompatibility Antigens Class II); 0 (Receptors, Antigen, T-Cell, alpha-beta); 0 (Superantigens); 39424-53-8 (enterotoxin B, staphylococcal)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180127
[Lr] Data última revisão:
180127
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601991


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[PMID]:27770815
[Au] Autor:Lu S; Shi G; Xu X; Wang G; Lan X; Sun P; Li X; Zhang B; Gu X; Ichim TE; Wang H
[Ad] Endereço:Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
[Ti] Título:Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice.
[So] Source:J Transl Med;14(1):300, 2016 10 22.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl )-induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl . Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl induction. RESULTS: ERC treatment effectively decreased the CCl -induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4 and CD8 T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4 CD25 FOXP3 regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1ß, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. CONCLUSIONS: Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.
[Mh] Termos MeSH primário: Endométrio/citologia
Endométrio/transplante
Fígado/lesões
Fígado/patologia
[Mh] Termos MeSH secundário: Adulto
Animais
Antígenos CD/metabolismo
Tetracloreto de Carbono
Proliferação Celular
Citocinas/metabolismo
Feminino
Hepatócitos/patologia
Antígenos de Histocompatibilidade Classe II/metabolismo
Seres Humanos
Fígado/imunologia
Fígado/fisiopatologia
Testes de Função Hepática
Masculino
Camundongos Endogâmicos C57BL
Infiltração de Neutrófilos
Compostos Orgânicos/metabolismo
Regeneração
Baço/patologia
Linfócitos T Reguladores/imunologia
Regulação para Cima
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Cytokines); 0 (Histocompatibility Antigens Class II); 0 (Organic Chemicals); 0 (PKH 26); CL2T97X0V0 (Carbon Tetrachloride)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28851810
[Au] Autor:DeBerge M; Yeap XY; Dehn S; Zhang S; Grigoryeva L; Misener S; Procissi D; Zhou X; Lee DC; Muller WA; Luo X; Rothlin C; Tabas I; Thorp EB
[Ad] Endereço:From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.)
[Ti] Título:MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury.
[So] Source:Circ Res;121(8):930-940, 2017 Sep 29.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking. OBJECTIVE: We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion. METHODS AND RESULTS: In humans, we discovered that clinical reperfusion after myocardial infarction led to significant elevation of the soluble form of MerTK (myeloid-epithelial-reproductive tyrosine kinase; ie, soluble MER), a critical biomarker of compromised phagocytosis by innate macrophages. In reperfused mice, macrophage deficiency led to decreased cardiac wound debridement, increased infarct size, and depressed cardiac function, newly implicating MerTK in cardiac repair after myocardial ischemia reperfusion. More notably, ) mice, which are resistant to cleavage, showed significantly reduced infarct sizes and improved systolic function. In contrast to other cardiac phagocyte subsets, resident cardiac MHCII CCR2 (major histocompatibility complex II/C-C motif chemokine receptor type 2) macrophages expressed higher levels of MerTK and, when exposed to apoptotic cells, secreted proreparative cytokines, including transforming growth factor-ß. deficiency compromised the accumulation of MHCII phagocytes, and this was rescued in ) mice. Interestingly, blockade of CCR2-dependent monocyte infiltration into the heart reduced soluble MER levels post-ischemia reperfusion. CONCLUSIONS: Our data implicate monocyte-induced MerTK cleavage on proreparative MHCII cardiac macrophages as a novel contributor and therapeutic target of reperfusion injury.
[Mh] Termos MeSH primário: Macrófagos/enzimologia
Traumatismo por Reperfusão Miocárdica/enzimologia
Miocárdio/enzimologia
Proteínas Proto-Oncogênicas/metabolismo
Receptores Proteína Tirosina Quinases/metabolismo
Infarto do Miocárdio com Supradesnível do Segmento ST/enzimologia
[Mh] Termos MeSH secundário: Animais
Apoptose
Citocinas/imunologia
Citocinas/metabolismo
Modelos Animais de Doenças
Feminino
Predisposição Genética para Doença
Antígenos de Histocompatibilidade Classe II/imunologia
Antígenos de Histocompatibilidade Classe II/metabolismo
Seres Humanos
Imunidade Inata
Macrófagos/imunologia
Macrófagos/patologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Meia-Idade
Monócitos/enzimologia
Monócitos/imunologia
Traumatismo por Reperfusão Miocárdica/imunologia
Traumatismo por Reperfusão Miocárdica/patologia
Traumatismo por Reperfusão Miocárdica/fisiopatologia
Miocárdio/imunologia
Miocárdio/patologia
Fagocitose
Fenótipo
Proteólise
Proteínas Proto-Oncogênicas/deficiência
Proteínas Proto-Oncogênicas/genética
Proteínas Proto-Oncogênicas/imunologia
Receptores Proteína Tirosina Quinases/deficiência
Receptores Proteína Tirosina Quinases/genética
Receptores Proteína Tirosina Quinases/imunologia
Receptores CCR2/genética
Receptores CCR2/imunologia
Receptores CCR2/metabolismo
Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia
Infarto do Miocárdio com Supradesnível do Segmento ST/patologia
Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia
Transdução de Sinais
Fatores de Tempo
c-Mer Tirosina Quinase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ccr2 protein, mouse); 0 (Cytokines); 0 (Histocompatibility Antigens Class II); 0 (Proto-Oncogene Proteins); 0 (Receptors, CCR2); EC 2.7.10.1 (MERTK protein, human); EC 2.7.10.1 (Mertk protein, mouse); EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases); EC 2.7.10.1 (c-Mer Tyrosine Kinase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170831
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.117.311327


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[PMID]:28832681
[Au] Autor:Lee J; Tam H; Adler L; Ilstad-Minnihan A; Macaubas C; Mellins ED
[Ad] Endereço:Department of Pediatrics, Program in Immunology, Stanford University, Stanford, California, United States of America.
[Ti] Título:The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines.
[So] Source:PLoS One;12(8):e0183594, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monocytes play a critical role in the innate and adaptive immune systems, performing phagocytosis, presenting antigen, and producing cytokines. They are a heterogeneous population that has been divided in humans into classical, intermediate, and non-classical subsets, but the roles of these subsets are incompletely understood. In this study, we investigated the expression patterns of MHC class II (MHCII) and associated molecules and find that the intermediate monocytes express the highest levels of the MHC molecules, HLA-DR (tested in n = 30 samples), HLA-DP (n = 30), and HLA-DQ (n = 10). HLA-DM (n = 30), which catalyzes the peptide exchange on the MHC molecules, is also expressed at the highest levels in intermediate monocytes. To measure HLA-DM function, we measured levels of MHCII-bound CLIP (class II invariant chain peptide, n = 23), which is exchanged for other peptides by HLA-DM. We calculated CLIP:MHCII ratios to normalize CLIP levels to MHCII levels, and found that intermediate monocytes have the lowest CLIP:MHCII ratio. We isolated the different monocyte subsets (in a total of 7 samples) and analyzed their responses to selected cytokines as model of monocyte activation: two M1-polarizing cytokines (IFNγ, GM-CSF), an M2-polarizing cytokine (IL-4) and IL-10. Classical monocytes exhibit the largest increases in class II pathway expression in response to stimulatory cytokines (IFNγ, GM-CSF, IL-4). All three subsets decrease HLA-DR levels after IL-10 exposure. Our findings argue that intermediate monocytes are the most efficient constitutive antigen presenting subset, that classical monocytes are recruited into an antigen presentation role during inflammatory responses and that IL-10 negatively regulates this function across all subsets.
[Mh] Termos MeSH primário: Citocinas/fisiologia
Antígenos de Histocompatibilidade Classe II/imunologia
Monócitos/imunologia
[Mh] Termos MeSH secundário: Adulto
Citometria de Fluxo
Seres Humanos
Subpopulações de Linfócitos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Histocompatibility Antigens Class II)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183594


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[PMID]:28822268
[Au] Autor:Mangale V; Marro BS; Plaisted WC; Walsh CM; Lane TE
[Ad] Endereço:Department of Pathology, Division of Microbiology & Immunology University of Utah, Salt Lake City, UT 84112, United States.
[Ti] Título:Neural precursor cells derived from induced pluripotent stem cells exhibit reduced susceptibility to infection with a neurotropic coronavirus.
[So] Source:Virology;511:49-55, 2017 Nov.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The present study examines the susceptibility of mouse induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) to infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Similar to NPCs derived from striatum of day 1 postnatal GFP-transgenic mice (GFP-NPCs), iPSC-derived NPCs (iPSC-NPCs) are able to differentiate into terminal neural cell types and express MHC class I and II in response to IFN-γ treatment. However, in contrast to postnatally-derived NPCs, iPSC-NPCs express low levels of carcinoembryonic antigen-cell adhesion molecule 1a (CEACAM1a), the surface receptor for JHMV, and are less susceptible to infection and virus-induced cytopathic effects. The relevance of this in terms of therapeutic application of NPCs resistant to viral infection is discussed.
[Mh] Termos MeSH primário: Diferenciação Celular
Células-Tronco Pluripotentes Induzidas/fisiologia
Vírus da Hepatite Murina/crescimento & desenvolvimento
Vírus da Hepatite Murina/imunologia
Células-Tronco Neurais/imunologia
Células-Tronco Neurais/virologia
[Mh] Termos MeSH secundário: Animais
Antígeno Carcinoembrionário/biossíntese
Expressão Gênica
Antígenos de Histocompatibilidade Classe I/biossíntese
Antígenos de Histocompatibilidade Classe II/biossíntese
Interferon gama/metabolismo
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carcinoembryonic Antigen); 0 (Ceacam1 protein, mouse); 0 (Histocompatibility Antigens Class I); 0 (Histocompatibility Antigens Class II); 82115-62-6 (Interferon-gamma)
[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:170820
[St] Status:MEDLINE


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[PMID]:28813660
[Au] Autor:Denzin LK; Khan AA; Virdis F; Wilks J; Kane M; Beilinson HA; Dikiy S; Case LK; Roopenian D; Witkowski M; Chervonsky AV; Golovkina TV
[Ad] Endereço:Child Health Institute of NJ, Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of NJ, New Brunswick, NJ 08901, USA.
[Ti] Título:Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-classical MHC Class II Gene H2-Ob.
[So] Source:Immunity;47(2):310-322.e7, 2017 Aug 15.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Select humans and animals control persistent viral infections via adaptive immune responses that include production of neutralizing antibodies. The precise genetic basis for the control remains enigmatic. Here, we report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype. Subsequent bioinformatics and functional analyses of the human H2-Ob homolog, HLA-DOB, revealed both loss- and gain-of-function alleles, which could affect the ability of their carriers to control infections with human hepatitis B (HBV) and C (HCV) viruses. Thus, understanding of the previously unappreciated role of H2-O (HLA-DO) in immunity to infections may suggest new approaches in achieving neutralizing immunity to viruses.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes
Antígenos HLA-D/metabolismo
Antígenos de Histocompatibilidade Classe II/metabolismo
Imunidade Humoral
Vírus do Tumor Mamário do Camundongo/imunologia
Vírus Rauscher/imunologia
Infecções por Retroviridae/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/metabolismo
Anticorpos Antivirais/metabolismo
Apresentação do Antígeno/genética
Biologia Computacional
Feminino
Predisposição Genética para Doença
Antígenos HLA-D/genética
Células HeLa
Hepatite B/imunologia
Hepatite B/transmissão
Hepatite C/imunologia
Hepatite C/transmissão
Antígenos de Histocompatibilidade Classe II/genética
Seres Humanos
Imunidade Humoral/genética
Masculino
Camundongos
Camundongos Endogâmicos
Camundongos Knockout
Mutação/genética
Polimorfismo Genético
Infecções por Retroviridae/transmissão
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (H-2O antigen); 0 (HLA-D Antigens); 0 (HLA-DO antigens); 0 (Histocompatibility Antigens Class II)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE


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[PMID]:28782517
[Au] Autor:Suárez CF; Pabón L; Barrera A; Aza-Conde J; Patarroyo MA; Patarroyo ME
[Ad] Endereço:Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá D.C., Colombia; Universidad del Rosario, Bogotá D.C., Colombia; Universidad de Ciencias Aplicadas y Ambientales (UDCA), Bogotá, Colombia.
[Ti] Título:Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans.
[So] Source:Biochem Biophys Res Commun;491(4):1062-1069, 2017 Sep 30.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:More than 50 years ago the owl monkey (genus Aotus) was found to be highly susceptible to developing human malaria, making it an excellent experimental model for this disease. Microbes and parasites' (especially malaria) tremendous genetic variability became resolved during our malaria vaccine development, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPs are immunologically silent and must be specially modified (mHABPs) to induce a perfect fit into major histocompatibility complex (MHC) molecules (HLA in humans). Since malarial immunity is mainly antibody-mediated and controlled by the HLA-DRB genetic region, ∼1000 Aotus have been molecularly characterised for MHC-DRB, revealing striking similarity between human and Aotus MHC-DRB repertories. Such convergence suggested that a large group of immune protection-inducing protein structures (IMPIPS), highly immunogenic and protection inducers against malarial intravenous challenge in Aotus, could easily be used in humans for inducing full protection against malaria. We highlight the value of a logical and rational methodology for developing a vaccine in an appropriate animal model: Aotus monkeys.
[Mh] Termos MeSH primário: Antígenos de Histocompatibilidade Classe II/química
Antígenos de Histocompatibilidade Classe II/imunologia
Vacinas Antimaláricas/química
Vacinas Antimaláricas/imunologia
[Mh] Termos MeSH secundário: Animais
Reações Antígeno-Anticorpo
Aotidae
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histocompatibility Antigens Class II); 0 (Malaria Vaccines)
[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:170808
[St] Status:MEDLINE


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[PMID]:28756073
[Au] Autor:Renauer P; Sawalha AH
[Ad] Endereço:University of Michigan, department of internal medicine, division of rheumatology, Ann Arbor, MI, USA.
[Ti] Título:The genetics of Takayasu arteritis.
[So] Source:Presse Med;46(7-8 Pt 2):e179-e187, 2017 Jul - Aug.
[Is] ISSN:2213-0276
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Takayasu arteritis (TAK) is a rare systemic vasculitis that is characterized by granulomatous inflammation of the aorta and its major branches. The cellular and biochemical processes involved in the pathogenesis of TAK are beginning to be elucidated, and implicate both cell and antibody-mediated autoimmune mechanisms. In addition, the underlying etiology to TAK may be explained, at least in part, by a complex genetic contribution. The most well-recognized genetic susceptibility locus for the disease is the classical HLA allele, HLA-B*52, which has been confirmed in several ethnicities. The genetic susceptibility with HLA-B*52, as well as additional classical alleles and loci, implicate both HLA class I and class II involvement in TAK. Furthermore, genetic associations with genes encoding immune response regulators, pro-inflammatory cytokines and mediators of humoral immunity may directly relate to disease mechanisms. Non-HLA susceptibility loci that have been recently established for TAK with a genome-wide level of significance include FCGR2A/FCGR3A, IL12B, IL6, RPS9/LILRB3, and a locus on chromosome 21 near PSMG1. In this review, we present the complex genetic predisposition to TAK and discuss how recent findings identified potential targets in the pathogenesis and treatment of the disease.
[Mh] Termos MeSH primário: Arterite de Takayasu/genética
[Mh] Termos MeSH secundário: Alelos
Antígenos CD/genética
Predisposição Genética para Doença
Antígenos de Histocompatibilidade Classe I/genética
Antígenos de Histocompatibilidade Classe II/genética
Seres Humanos
Subunidade p40 da Interleucina-12/genética
Interleucina-6/genética
Receptores de IgG/genética
Receptores Imunológicos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (FCGR2A protein, human); 0 (Histocompatibility Antigens Class I); 0 (Histocompatibility Antigens Class II); 0 (IL12B protein, human); 0 (Interleukin-12 Subunit p40); 0 (Interleukin-6); 0 (LILRB3 protein, human); 0 (Receptors, IgG); 0 (Receptors, Immunologic)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170731
[St] Status:MEDLINE



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