Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.014
Filtrar
1.
Signal Transduct Target Ther ; 5(1): 192, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895366

Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Regulação da Expressão Gênica/imunologia , Linfopenia/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/genética , Infecções por Coronavirus/mortalidade , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/mortalidade , Progressão da Doença , Feminino , Receptor Celular 2 do Vírus da Hepatite A/sangue , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/sangue , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Contagem de Linfócitos , Linfopenia/diagnóstico , Linfopenia/genética , Linfopenia/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/genética , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Linfócitos T/virologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
2.
Signal Transduct Target Ther ; 5(1): 192, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: covidwho-748172

Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Regulação da Expressão Gênica/imunologia , Linfopenia/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/genética , Infecções por Coronavirus/mortalidade , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/mortalidade , Progressão da Doença , Feminino , Receptor Celular 2 do Vírus da Hepatite A/sangue , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/sangue , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Contagem de Linfócitos , Linfopenia/diagnóstico , Linfopenia/genética , Linfopenia/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/genética , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Linfócitos T/virologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
3.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1323-1333, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32748590

RESUMO

The aim of this study was to investigate the expression of MHCⅠ gene in different tissues of Rana dybowskii under the stress of Aeromonas hydrophila (Ah), and to provide evidence for revealing the anti-infective immune response mechanism of amphibians. The experimental animal model of Aeromonas hydrophila infection was first constructed, and the pathological changes were observed by HE staining. The MHCⅠ gene α1+α2 peptide binding region of Rana dybowskii was cloned by RT-PCR and analyzed by bioinformatics. Real-time PCR was used to detect the transcription level of MHCⅠ in different tissues under Ah stress. After Ah infection, the skin, liver and muscle tissues showed signs of cell structure disappearance and texture disorder. The MHCⅠ gene α1+α2 peptide binding region fragment was 494 bp, encoding 164 amino acids, and homology with amphibians. Above 77%, the homology with mammals was as low as 14.96%, indicating that the α1+α2 region of MHC gene was less conserved among different species. The results of real-time PCR show that the liver, spleen and kidney of the experimental group were under Ah stress. The transcript levels of MHCⅠ gene in skin and muscle tissues were higher than those in the control group at 72 h, but the time to peak of each tissue was different (P<0.01), indicating that the response time of MHCⅠ gene in different tissues was different under Ah stress. This study provides a reference for further exploring the immune function of MHC molecules in anti-infection.


Assuntos
Aeromonas hydrophila , Regulação da Expressão Gênica , Infecções por Bactérias Gram-Negativas , Ranidae , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Fígado/metabolismo , Ranidae/genética , Ranidae/imunologia , Ranidae/microbiologia , Pele/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-32656652

RESUMO

Vibrio alginolyticus is posting an increasing threat to survival of grouper. Classical complement cascade can trigger initiation of immunity, while complement 9 (C9) is a major complement molecule involved in final step of membrane attack complex (MAC) formation. In this study, full-length EcC9 contained an ORF sequence of 1779 bp, encoding a polypeptide of 592 amino acids. A high-level expression of EcC9 mRNA was observed in liver. Following vibrio challenge, increased expression levels of EcC1q, EcBf/C2, EcC4, EcC6, EcC7 and EcC9 mRNA were detected in liver and kidney. These results implied that elevated expression level of classical complement pathway (CCP) and terminal complement components (TCCs) may assess toxicological effect of V. alginolyticus.


Assuntos
Bass/genética , Bass/imunologia , Complemento C9/genética , Complemento C9/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Complemento C9/química , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Filogenia , Alinhamento de Sequência/veterinária , Vibrio alginolyticus/fisiologia
5.
Arch Virol ; 165(10): 2249-2258, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32696270

RESUMO

While infectious bursal disease virus (IBDV) mainly targets immature B cells and causes T cell infiltration in the bursa of Fabricius (BF) of chickens, the effect of IBDV infection on the properties of T cells and relevant cytokine production in avian gut-associated lymphoid tissues (GALTs) remains unknown. Here, we show that while the CD8+ T cell subset is not affected, IBDV infection decreases the percentage of CD4+ T cells in the cecal tonsil (CT), but not in esophagus tonsil, pylorus tonsil, and Meckel's diverticulum of GALTs, in contrast to BF and spleen, in which the proportion of CD4+ cells increases upon IBDV infection. Further, IBDV infection upregulates IFN-γ, IL-10, and the T cell checkpoint receptor LAG-3 mRNA expression in BF. In contrast, in CTs, IBDV infection significantly increases the production of IFN-ß and CTLA-4 mRNA, while no significant effect is seen in the case of IFN-γ, IL-10 and LAG-3. Together, our data reveal differential modulation of T cell subsets and proinflammatory cytokine production in different lymphoid tissues during the course of IBDV infection.


Assuntos
Subpopulações de Linfócitos B/imunologia , Infecções por Birnaviridae/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Regulação da Expressão Gênica/imunologia , Doenças das Aves Domésticas/imunologia , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Subpopulações de Linfócitos B/virologia , Infecções por Birnaviridae/genética , Infecções por Birnaviridae/patologia , Infecções por Birnaviridae/virologia , Bolsa de Fabricius/imunologia , Bolsa de Fabricius/virologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Galinhas/virologia , Vírus da Doença Infecciosa da Bursa/crescimento & desenvolvimento , Vírus da Doença Infecciosa da Bursa/imunologia , Vírus da Doença Infecciosa da Bursa/patogenicidade , Interferon beta/genética , Interferon beta/imunologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/virologia , Tonsila Palatina/imunologia , Tonsila Palatina/virologia , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/patologia , Doenças das Aves Domésticas/virologia
6.
Mol Immunol ; 125: 32-42, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32629323

RESUMO

Compelling evidence has demonstrated that Th17 cells play an essential role in the pathogenesis of multiple sclerosis (MS). Long noncoding RNAs (lncRNAs) have been confirmed as vital regulators of immune cell differentiation and other functions. However, whether and how lncRNAs influence Th17 cell differentiation and functional behaviors remain largely unclear. Here, we identified that a lncRNA, namely Gm15575, is specifically enriched in Th17 cells and spleen tissues of EAE mice. Functionally, knockdown of Gm15575 in Th17 cells suppressed the secretion of IL17A. Mechanistically, Gm15575 served as a competing endogenous RNA (ceRNA) to block the function of miR-686, positively regulating the expression of CCL7, a pro-inflammatory chemokine with high expression in Th17 cells, and Th17 differentiation. Taken together, our study revealed that Gm15575-miR-686 axis promoted the progression of EAE by regulating Th17 differentiation and expression of CCL7 which elucidated the pathogenesis of autoimmune diseases at genetic level. Gm15575 can be involved in the course of Th17-related autoimmune diseases.


Assuntos
Quimiocina CCL7/biossíntese , Encefalomielite Autoimune Experimental/genética , Regulação da Expressão Gênica/imunologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Células Th17/imunologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Quimiocina CCL7/genética , Quimiocina CCL7/imunologia , Encefalomielite Autoimune Experimental/imunologia , Camundongos , MicroRNAs/imunologia , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , RNA Longo não Codificante/imunologia , Regulação para Cima
7.
Nat Commun ; 11(1): 3548, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669541

RESUMO

Congenital CMV infection (cCMVi) affects 0.5-1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.


Assuntos
Infecções por Citomegalovirus/sangue , Citomegalovirus/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Perda Auditiva Neurossensorial/epidemiologia , Infecções Assintomáticas , Biomarcadores/sangue , Estudos de Casos e Controles , Pré-Escolar , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Feminino , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/imunologia , Perda Auditiva Neurossensorial/virologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Transcriptoma/genética
8.
Nature ; 583(7815): 296-302, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32612232

RESUMO

The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens1. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity2. However, immune functions are not unique to haematopoietic cells, and many other cell types display basic mechanisms of pathogen defence3-5. To advance our understanding of immunology outside the haematopoietic system, here we systematically investigate the regulation of immune genes in the three major types of structural cells: epithelium, endothelium and fibroblasts. We characterize these cell types across twelve organs in mice, using cellular phenotyping, transcriptome sequencing, chromatin accessibility profiling and epigenome mapping. This comprehensive dataset revealed complex immune gene activity and regulation in structural cells. The observed patterns were highly organ-specific and seem to modulate the extensive interactions between structural cells and haematopoietic immune cells. Moreover, we identified an epigenetically encoded immune potential in structural cells under tissue homeostasis, which was triggered in response to systemic viral infection. This study highlights the prevalence and organ-specific complexity of immune gene activity in non-haematopoietic structural cells, and it provides a high-resolution, multi-omics atlas of the epigenetic and transcriptional networks that regulate structural cells in the mouse.


Assuntos
Endotélio/imunologia , Células Epiteliais/imunologia , Fibroblastos/imunologia , Regulação da Expressão Gênica/imunologia , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Especificidade de Órgãos/imunologia , Imunidade Adaptativa , Animais , Cromatina/genética , Cromatina/metabolismo , Endotélio/citologia , Epigênese Genética/imunologia , Epigenoma/genética , Células Epiteliais/citologia , Feminino , Fibroblastos/citologia , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/imunologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Sistema Imunitário/virologia , Imunidade Inata , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/imunologia , Masculino , Camundongos , Especificidade de Órgãos/genética , Transcrição Genética/imunologia , Transcriptoma/genética
9.
Mol Immunol ; 124: 142-152, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32563859

RESUMO

Long noncoding RNAs (lncRNAs) play an indispensable role in the process of M1 macrophage via regulating the development of macrophages and their responses to bacterial pathogens and viral infections. However, there are few studies on the lncRNA-mediated functions and regulatory mechanisms of M2 macrophage polarization. In this study, we found a number of differentially expressed lncRNAs between human monocyte derived M0 and M2 macrophages according to array analysis and quantitative polymerase chain reaction (qPCR) validation. The lncRNA RP11-389C8.2 (we named lnc-M2 in this study) was observed to be highly expressed in M2 macrophages. In Situ Localization and Quantification Analysis showed that lnc-M2 was expressed in the nucleus and cytosolic compartments of M2 macrophages. Notably, lnc-M2 knockdown enhanced the phagocytic ability of M2 macrophages. Ulteriorly, the results of RNA-Protein interaction experiments indicated that protein kinase A (PKA) was a lnc-M2 associated RNA-binding protein (RBP). Western blot showed that phosphorylated cAMP response element binding protein (p-CREB), a well-known key downstream transcription factor of PKA, was lowly phosphorylated in lnc-M2-silencing M2 macrophages. Furthermore, we found that transcriptional factor Signal Transducer And Activator Of Transcription 3 (STAT3) promoted lnc-M2 transcription along with the up-regulation of epigenetic histone modification markers at the lnc-M2 promoter locus, indicating that STAT3 activated lnc-M2 and eventually facilitated the process of M2 macrophage differentiation via the PKA/CREB pathway. Collectively, our date provide evidence that the transcription factor STAT3 can promote the transcription of lnc-M2 and facilitated the process of M2 macrophage differentiation via the PKA/CREB pathway. This study highlights a novel mechanism underlying the M2 macrophage differentiation.


Assuntos
Regulação da Expressão Gênica/imunologia , Ativação de Macrófagos/genética , Macrófagos/imunologia , RNA Longo não Codificante/genética , Diferenciação Celular/genética , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Macrófagos/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/imunologia
10.
Mol Immunol ; 124: 1-8, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32480291

RESUMO

Regulatory T cells (Tregs) is one of the immunosuppressive subsets of CD4+ T cells characterized by transcription factor forkhead box protein P3 (FOXP3) expression which are involved in tumor development and progression. Identification of the factors that influence Treg cell function is extremely important. Our current study aimed to evaluate the frequency of Treg cells, cytokine secretion and the expression of microRNAs (miRNAs) in pediatric acute lymphoblastic leukemia (ALL) patients. The frequency of CD3+, CD4+ and CD4+CD25+FOXP3+ Treg was assessed by flow cytometry in 43 ALL patients versus 42 controls. Plasma levels of IL-10, transcription factor ß (TGF-ß), IL-6, IL-17, IL-23 and tumor necrosis factor (TNF-α) were measured by Enzyme-linked immunosorbent assay (ELISA). miR-21, miR-24, miR-26a, miR133b, miR-148a and miR-155 expression were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). A slight insignificant increase in Treg cells in ALL patients compared to controls was observed. There was a significant elevation in IL-10 (p < 0.05), IL-6 (p < 0.01), IL-23 (p < 0.05) and TNF-α (p < 0.01) in ALL patients compared with controls. Meanwhile, a significant reduction in TGF-ß (p < 0.001) was recorded. A slight insignificant decrease in IL-17 in ALL patients was observed.ALL patients showed a significant increase in miR-21 (p < 0.05), miR-148a (p < 0.01), miR-24 (p < 0.05) and a significant reduction in miR-155 (p < 0.01). In conclusion, the slight change in Treg cells frequency and alteration in related cytokines could possibly involve in the pathogenesis of ALL. Dysregulated miRNAs, as a regulatory mechanism of epigenetics, might contribute to these observed results. Further researches are required to confirm our interesting findings.


Assuntos
Citocinas/imunologia , MicroRNAs/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Linfócitos T Reguladores/imunologia , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Lactente , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
11.
PLoS Genet ; 16(6): e1008861, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32525870

RESUMO

In metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). Expression of genomic TEs is proposed to initiate self regulation by increasing the production of repressive piRNAs, thereby "adapting" piRNA-mediated control to the most active TE families. Surprisingly, however, piRNA pathway proteins, which execute piRNA biogenesis and enforce silencing of targeted sequences, evolve rapidly and adaptively in animals. If TE silencing is ensured through piRNA biogenesis, what necessitates changes in piRNA pathway proteins? Here we used interspecific complementation to test for functional differences between Drosophila melanogaster and D. simulans alleles of three adaptively evolving piRNA pathway proteins: Armitage, Aubergine and Spindle-E. In contrast to piRNA-mediated transcriptional regulators examined in previous studies, these three proteins have cytoplasmic functions in piRNA maturation and post-transcriptional silencing. Across all three proteins we observed interspecific divergence in the regulation of only a handful of TE families, which were more robustly silenced by the heterospecific piRNA pathway protein. This unexpected result suggests that unlike transcriptional regulators, positive selection has not acted on cytoplasmic piRNA effector proteins to enhance their function in TE repression. Rather, TEs may evolve to "escape" silencing by host proteins. We further discovered that D. simulans alleles of aub and armi exhibit enhanced off-target effects on host transcripts in a D. melanogaster background, as well as modest reductions in the efficiency of piRNA biogenesis, suggesting that promiscuous binding of D. simulans Aub and Armi proteins to host transcripts reduces their participation in piRNA production. Avoidance of genomic auto-immunity may therefore be a critical target of selection. Our observations suggest that piRNA effector proteins are subject to an evolutionary trade-off between defending the host genome from the harmful effect of TEs while also minimizing collateral damage to host genes.


Assuntos
Autoimunidade/genética , Elementos de DNA Transponíveis/imunologia , Drosophila simulans/genética , Evolução Molecular , Genoma de Inseto/imunologia , RNA Interferente Pequeno/biossíntese , Alelos , Animais , Animais Geneticamente Modificados , Citoplasma/genética , Citoplasma/metabolismo , Elementos de DNA Transponíveis/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/imunologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/imunologia , Drosophila melanogaster/metabolismo , Drosophila simulans/metabolismo , Feminino , Regulação da Expressão Gênica/imunologia , Genoma de Inseto/genética , Masculino , Mutação , Interferência de RNA/imunologia
14.
J Vet Sci ; 21(3): e50, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476323

RESUMO

BACKGROUND: Porcine parvovirus (PPV) is a single-stranded DNA virus that causes porcine reproductive failure. It is of critical importance to study PPV pathogenesis for the prevention and control of the disease. NS1, a PPV non-structural protein, is participated in viral DNA replication, transcriptional regulation, and cytotoxicity. Our previous research showed that PPV can activate nuclear factor kappa B (NF-κB) signaling pathway and then up-regulate the expression of interleukin (IL)-6. OBJECTIVES: Herein, the purpose of this study is to determine whether the non-structural protein NS1 of PPV also has the same function. METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, western blot, immunofluorescence assay and small interfering RNA (siRNA) were used. RESULTS: Our findings demonstrated that PPV NS1 protein can up-regulate the expression levels of IL-6 and tumor necrosis factor-alpha in a dose-dependent manner. Moreover, PPV NS1 protein was found to induce the phosphorylation of IκBα, then leading to the phosphorylation and nuclear translocation of NF-κB. In addition, the NS1 protein activated the upstream pathways of NF-κB. Meanwhile, TLR2-siRNA assay showed TLR2 plays an important role in the activation of NF-κB signaling pathway induced by PPV-NS1. CONCLUSIONS: These findings indicated that PPV NS1 protein induced the up-regulated of IL-6 expression through activating the TLR2 and NF-κB signaling pathways. In conclusion, these findings provide a new avenue to study the innate immune mechanism of PPV infection.


Assuntos
NF-kappa B/metabolismo , Infecções por Parvoviridae/veterinária , Parvovirus Suíno/fisiologia , Transdução de Sinais , Doenças dos Suínos/genética , Receptor 2 Toll-Like/metabolismo , Proteínas não Estruturais Virais/genética , Animais , Regulação da Expressão Gênica/imunologia , NF-kappa B/genética , Infecções por Parvoviridae/genética , Infecções por Parvoviridae/metabolismo , Parvovirus Suíno/genética , Suínos , Doenças dos Suínos/metabolismo , Receptor 2 Toll-Like/genética , Proteínas não Estruturais Virais/metabolismo
15.
Nat Immunol ; 21(7): 777-789, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32572238

RESUMO

T follicular helper (TFH) cells are a distinct type of CD4+ T cells that are essential for most antibody and B lymphocyte responses. TFH cell regulation and dysregulation is involved in a range of diseases. Bcl-6 is the lineage-defining transcription factor of TFH cells and its activity is essential for TFH cell differentiation and function. However, how Bcl-6 controls TFH biology has largely remained unclear, at least in part due to the intrinsic challenges of connecting repressors to gene upregulation in complex cell types with multiple possible differentiation fates. Multiple competing models were tested here by a series of experimental approaches to determine that Bcl-6 exhibits negative autoregulation and controls pleiotropic attributes of TFH differentiation and function, including migration, costimulation, inhibitory receptors and cytokines, via multiple repressor-of-repressor gene circuits.


Assuntos
Regulação da Expressão Gênica/imunologia , Centro Germinativo/imunologia , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Proteínas Repressoras/genética , Linfócitos T Auxiliares-Indutores/imunologia , Transferência Adotiva , Animais , Sistemas CRISPR-Cas/genética , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular , Movimento Celular/genética , Movimento Celular/imunologia , Sequenciamento de Cromatina por Imunoprecipitação , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Redes Reguladoras de Genes , Centro Germinativo/citologia , Humanos , Masculino , Camundongos , Mutação , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , RNA-Seq , Proteínas Repressoras/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
18.
Immunogenetics ; 72(5): 315-323, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32556497

RESUMO

Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.


Assuntos
Dermatite Atópica/veterinária , Doenças do Cão/genética , Regulação da Expressão Gênica/imunologia , Pele/imunologia , Animais , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Doenças do Cão/imunologia , Cães , Inflamação/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma
19.
Nat Commun ; 11(1): 2611, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457298

RESUMO

Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program. Our results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Transtornos Relacionados ao Uso de Opioides/imunologia , Viroses/imunologia , Adulto , Antivirais/farmacologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interferons/farmacologia , Leucócitos Mononucleares , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Morfina/farmacologia , Análise de Célula Única , Adulto Jovem
20.
Nat Commun ; 11(1): 2198, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366944

RESUMO

The thymus supports multiple αß T cell lineages that are functionally distinct, but mechanisms that control this multifaceted development are poorly understood. Here we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEClow subsets distinguished by surface, intracellular and secreted molecules, and identify LTßR as a cell-autonomous controller of their development. Importantly, this mTEC heterogeneity enables the thymus to differentially control iNKT sublineages possessing distinct effector properties. mTEC expression of LTßR is essential for the development thymic tuft cells which regulate NKT2 via IL-25, while LTßR controls CD104+CCL21+ mTEClow that are capable of IL-15-transpresentation for regulating NKT1 and NKT17. Finally, mTECs regulate both iNKT-mediated activation of thymic dendritic cells, and iNKT availability in extrathymic sites. In conclusion, mTEC specialization controls intrathymic iNKT cell development and function, and determines iNKT pool size in peripheral tissues.


Assuntos
Diferenciação Celular/imunologia , Células Epiteliais/imunologia , Células T Matadoras Naturais/imunologia , Timócitos/imunologia , Timo/imunologia , Animais , Antígenos CD1d/genética , Antígenos CD1d/imunologia , Antígenos CD1d/metabolismo , Diferenciação Celular/genética , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Proliferação de Células/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/imunologia , Ativação Linfocitária/imunologia , Receptor beta de Linfotoxina/genética , Receptor beta de Linfotoxina/imunologia , Receptor beta de Linfotoxina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células T Matadoras Naturais/citologia , Células T Matadoras Naturais/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Timócitos/citologia , Timócitos/metabolismo , Timo/citologia , Timo/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA