Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
J Allergy Clin Immunol ; 152(4): 972-983, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37343845

RESUMO

BACKGROUND: Gain-of-function variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy, and eosinophilia. OBJECTIVES: This study sought to describe the clinical and immunological characteristics associated with a new gain-of-function variant of JAK1 and report the therapeutic efficacy of Janus kinase (JAK) inhibition. METHODS: The investigators identified a family affected by JAK1-associated autoinflammatory disease and performed clinical assessment and immunological monitoring on 9 patients. JAK1 signaling was studied by flow and mass cytometry in patients' cells at basal state or after immune stimulation. A molecular disease signature in the blood was studied at the transcriptomic level. Patients were treated with 1 of 2 JAK inhibitors: either baricitinib or upadacitinib. Clinical, cellular, and molecular response were evaluated over a 2-year period. RESULTS: Affected individuals displayed a syndromic disease with prominent allergy including atopic dermatitis, ichthyosis, arthralgia, chronic diarrhea, disseminated calcifying fibrous tumors, and elevated whole blood histamine levels. A variant of JAK1 localized in the pseudokinase domain was identified in all 9 affected, tested patients. Hyper-phosphorylation of STAT3 was found in 5 of 6 patients tested. Treatment of patients' cells with baricitinib controlled most of the atypical hyper-phosphorylation of STAT3. Administration of baricitinib to patients led to rapid improvement of the disease in all adults and was associated with reduction of systemic inflammation. CONCLUSIONS: Patients with this new JAK1 gain-of-function pathogenic variant displayed very high levels of blood histamine and showed a variable combination of atopy with articular and gastrointestinal manifestations as well as calcifying fibrous tumors. The disease, which appears to be linked to STAT3 hyperactivation, was well controlled under treatment by JAK inhibitors in adult patients.


Assuntos
Dermatite Atópica , Inibidores de Janus Quinases , Neoplasias , Adulto , Humanos , Inibidores de Janus Quinases/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Histamina , Neoplasias/tratamento farmacológico , Janus Quinase 1/genética
2.
Front Immunol ; 12: 698808, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795661

RESUMO

Introduction: We analysed blood DNAemia of TTV and four herpesviruses (CMV, EBV, HHV6, and HSV-1) in the REAnimation Low Immune Status Marker (REALISM) cohort of critically ill patients who had presented with either sepsis, burns, severe trauma, or major surgery. The aim was to identify common features related to virus and injury-associated pathologies and specific features linking one or several viruses to a particular pathological context. Methods: Overall and individual viral DNAemia were measured over a month using quantitative PCR assays from the 377 patients in the REALISM cohort. These patients were characterised by clinical outcomes [severity scores, mortality, Intensive Care Unit (ICU)-acquired infection (IAI)] and 48 parameters defining their host response after injury (cell populations, immune functional assays, and biomarkers). Association between viraemic event and clinical outcomes or immune markers was assessed using χ2-test or exact Fisher's test for qualitative variables and Wilcoxon test for continuous variables. Results: The cumulative incidence of viral DNAemia increased from below 4% at ICU admission to 35% for each herpesvirus during the first month. EBV, HSV1, HHV6, and CMV were detected in 18%, 12%, 10%, and 9% of patients, respectively. The incidence of high TTV viraemia (>10,000 copies/ml) increased from 11% to 15% during the same period. Herpesvirus viraemia was associated with severity at admission; CMV and HHV6 viraemia correlated with mortality during the first week and over the month. The presence of individual herpesvirus during the first month was significantly associated (p < 0.001) with the occurrence of IAI, whilst herpesvirus DNAemia coupled with high TTV viraemia during the very first week was associated with IAI. Herpesvirus viraemia was associated with a lasting exacerbated host immune response, with concurrent profound immune suppression and hyper inflammation, and delayed return to immune homeostasis. The percentage of patients presenting with herpesvirus DNAemia was significantly higher in sepsis than in all other groups. Primary infection in the hospital and high IL10 levels might favour EBV and CMV reactivation. Conclusion: In this cohort of ICU patients, phenotypic differences were observed between TTV and herpesviruses DNAemia. The higher prevalence of herpesvirus DNAemia in sepsis hints at further studies that may enable a better in vivo understanding of host determinants of herpesvirus viral reactivation. Furthermore, our data suggest that EBV and TTV may be useful as additional markers to predict clinical deterioration in ICU patients.


Assuntos
Infecções por Vírus de DNA/epidemiologia , Infecções por Herpesviridae/epidemiologia , Herpesviridae/isolamento & purificação , Choque Séptico/etiologia , Torque teno virus/isolamento & purificação , Viremia/epidemiologia , Adulto , Idoso , Estado Terminal , Infecções por Vírus de DNA/complicações , Infecções por Vírus de DNA/virologia , Feminino , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/virologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Séptico/epidemiologia , Viremia/complicações , Viremia/virologia
4.
PLoS One ; 9(6): e97546, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24905099

RESUMO

OBJECTIVES: Community-acquired Staphylococcus aureus necrotizing pneumonia is a life-threatening disease. Panton Valentine Leukocidin (PVL) has been associated with necrotizing pneumonia. PVL triggers inflammasome activation in human macrophages leading to IL-1ß release. IL-1ß activates lung epithelial cells to release IL-8. This study aimed to assess the relevance of this inflammatory cascade in vivo and to test the potential of an IL-1 receptor antagonist (IL-1Ra/Kineret) to decrease inflammation-mediated lung injury. METHODS: We used the sequential instillation of Heat-killed S. aureus and PVL or S. aureus infection to trigger necrotizing pneumonia in rabbits. In these models, we investigated inflammation in the presence or absence of IL-1Ra/Kineret. RESULTS: We demonstrated that the presence of PVL was associated with IL-1ß and IL-8 release in the lung. During PVL-mediated sterile pneumonia, Kineret/IL-1Ra reduced IL-8 production indicating the relevance of the PVL/IL-1/IL-8 cascade in vivo and the potential of Kineret/IL-1Ra to reduce lung inflammation. However, Kineret/IL-1Ra was ineffective in blocking IL-8 production during infection with S. aureus. Furthermore, treatment with Kineret increased the bacterial burden in the lung. CONCLUSIONS: Our data demonstrate PVL-dependent inflammasome activation during S.aureus pneumonia, indicate that IL-1 signaling controls bacterial burden in the lung and suggest that therapy aimed at targeting this pathway might be deleterious during pneumonia.


Assuntos
Toxinas Bacterianas/toxicidade , Exotoxinas/toxicidade , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Leucocidinas/toxicidade , Pneumonia Estafilocócica/tratamento farmacológico , Animais , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Pneumonia Estafilocócica/etiologia , Pneumonia Estafilocócica/metabolismo , Coelhos
5.
Cell Microbiol ; 14(7): 1019-36, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22329718

RESUMO

Staphylococcus aureus is a major pathogen responsible for both nosocomial and community-acquired infections. Central to its virulence is its ability to secrete haemolysins, pore-forming toxins and cytolytic peptides. The large number of membrane-damaging toxins and peptides produced during S. aureus infections has hindered a precise understanding of their specific roles in diseases. Here, we used comprehensive libraries of recombinant toxins and synthetic cytolytic peptides, of S. aureus mutants and clinical strains to investigate the role of these virulence factors in targeting human macrophages and triggering IL-1ß release. We found that the Panton Valentine leukocidin (PVL) is the major trigger of IL-1ß release and inflammasome activation in primary human macrophages. The cytolytic peptides, δ-haemolysin and PSMα3; the pore-forming toxins, γ-haemolysin and LukDE; and ß-haemolysin synergize with PVL to amplify IL-1ß release, indicating that these factors cooperate with PVL to trigger inflammation. PVL(+) S. aureus causes necrotizing pneumonia in children and young adults. The severity of this disease is due to the massive recruitment of neutrophils that cause lung damage. Importantly, we demonstrate that PVL triggers IL-1ß release in human alveolar macrophages. Furthermore, IL-1ß released by PVL-intoxicated macrophages stimulates the secretion of the neutrophil attracting chemokines, IL-8 and monocyte chemotactic protein-1, by lung epithelial cells. Finally, we show that PVL-induced IL-8/monocyte chemotactic protein-1 release is abolished by the inclusion of IL-1 receptor antagonist (IL-1Ra) in a mixed culture of lung epithelial cells and macrophages. Together, our results identify PVL as the predominant S. aureus secreted factor for triggering inflammasome activation in human macrophages and demonstrate how PVL-intoxicated macrophages orchestrate inflammation in the lung. Finally, our work suggests that anakinra, a synthetic IL-1Ra, may be an effective therapeutic agent to reduce the massive neutrophils infiltration observed during necrotizing pneumonia and decrease the resulting host-mediated lung injury.


Assuntos
Toxinas Bacterianas/metabolismo , Quimiocinas/metabolismo , Células Epiteliais/imunologia , Exotoxinas/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Leucocidinas/metabolismo , Macrófagos/microbiologia , Staphylococcus aureus/patogenicidade , Animais , Criança , Humanos , Pulmão/imunologia , Pulmão/patologia , Macrófagos/imunologia , Neutrófilos/imunologia , Staphylococcus aureus/imunologia , Fatores de Virulência/metabolismo , Adulto Jovem
6.
J Gen Virol ; 91(Pt 1): 189-98, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19812268

RESUMO

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic, tick-borne member of the family Bunyaviridae and the genus Nairovirus. To better elucidate the pathogenesis of CCHFV, we analysed the host innate immune response induced in antigen-presenting cells (APCs) infected in vitro by CCHFV. Monocyte-derived dendritic cells (DCs) and macrophages (MPs) were both shown to be permissive for CCHFV and to replicate the virus, as monitored by genomic and antigenomic strand quantification. Virus replication was, however, controlled, corroborating an efficient alpha interferon-induced response. The upregulation of CD-83 and CD-86 indicated that CCHFV induced a partial maturation of DCs, which were also shown to activate the secretion of interleukin (IL)-6 and IL-8, but no tumour necrosis factor alpha (TNF-alpha). On the other hand, in MPs, CCHFV infection elicited a high IL-6 and TNF-alpha response and a moderate chemokine response. Nevertheless, when we compared these APC responses with those seen after infection with Dugbe virus (DUGV), a mildly pathogenic virus genetically close to CCHFV, we found that, in spite of some similarities, DUGV induced a higher cytokine/chemokine response in MPs. These results suggest that CCHFV is able to inhibit the activation of inflammatory mediators selectively in infection in vitro and that these differences could be relevant in pathogenesis.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/virologia , Regulação da Expressão Gênica , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/patogenicidade , Nairovirus/imunologia , Nairovirus/patogenicidade , Antígenos CD/biossíntese , Antígeno B7-2/biossíntese , Células Cultivadas , Quimiocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/virologia , Humanos , Imunoglobulinas/biossíntese , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Macrófagos/imunologia , Macrófagos/virologia , Glicoproteínas de Membrana/biossíntese , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima , Replicação Viral , Antígeno CD83
7.
Clin Vaccine Immunol ; 13(3): 409-14, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16522785

RESUMO

To evaluate the reactivity of the recombinant proteins expressed in Escherichia coli strain BL21(DE3), a Western blot assay was performed by using a panel of 78 serum samples obtained, respectively, from convalescent-phase patients infected with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) (30 samples) and from healthy donors (48 samples). As antigen for detection of SARS-CoV, the nucleocapsid protein (N) showed high sensitivity and strong reactivity with all samples from SARS-CoV patients and cross-reacted with all serum samples from healthy subjects, with either those obtained from China (10 samples) or those obtained from France (38 serum samples), giving then a significant rate of false positives. Specifically, our data indicated that the two subunits, S1 (residues 14 to 760) and S2 (residues 761 to 1190), resulted from the divided spike reacted with all samples from SARS-CoV patients and without any cross-reactivity with any of the healthy serum samples. Consequently, these data revealed the nonspecific nature of N protein in serodiagnosis of SARS-CoV compared with the S1 and S2, where the specificity is of 100%. Moreover, the reported results indicated that the use of one single protein as a detection antigen of SARS-CoV infection may lead to false-positive diagnosis. These may be rectified by using more than one protein for the serodiagnosis of SARS-CoV.


Assuntos
Anticorpos Antivirais/análise , Western Blotting/métodos , Glicoproteínas de Membrana/imunologia , Proteínas do Nucleocapsídeo/imunologia , Subunidades Proteicas/imunologia , Proteínas Recombinantes/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Proteínas do Envelope Viral/imunologia , Anticorpos Antivirais/biossíntese , Proteínas do Nucleocapsídeo de Coronavírus , Reações Falso-Positivas , Humanos , Proteínas do Nucleocapsídeo/biossíntese , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/isolamento & purificação , Subunidades Proteicas/biossíntese , Subunidades Proteicas/genética , Subunidades Proteicas/isolamento & purificação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus
8.
J Med Virol ; 78(2): 202-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16372286

RESUMO

HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown. Total RNA was extracted from liver biopsies of 12 HCV mono-infected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFNalpha, IFNgamma, TNFalpha, TGFbeta(1), IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach. Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons. Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNFalpha, IL-8, and IL-10 were statistically significant. Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV mono-infected persons, with the exception of TGFbeta1. These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver.


Assuntos
Citocinas/metabolismo , Regulação para Baixo , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/metabolismo , Biópsia , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Interleucina-10/metabolismo , Interleucina-8/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Masculino , Reação em Cadeia da Polimerase , RNA Viral/genética , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/metabolismo
9.
Hepatology ; 40(4): 900-9, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15382175

RESUMO

The hepatitis C virus (HCV) F protein is a recently described, frameshift product of HCV core encoding sequence of genotype 1a. Its function and antigenic properties are unknown. Using enzyme-linked immunosorbent assay, we assessed the prevalence of anti-F antibodies in 154 patients chronically infected with HCV, 65 patients with other liver diseases, and 121 healthy controls. For this purpose, we expressed a highly purified HCV F recombinant protein from HCV genotype 1a in Escherichia coli. Because the F protein shares the 10 first amino acids with the core protein, the anti-HCV F response was also assessed by a F recombinant protein deleted of its 10 first amino acids [Delta(1-10)-F]. Ninety-six (62%) of the 154 HCV serum samples reacted with the complete F recombinant protein, whereas 39 (25%) showed a weaker anti-Delta(1-10)F reactivity and 150 (97%) had anti-core antibodies. No reactivity against F, Delta(1-10)F, or core was detected in any of the controls. To exclude a potential cross-reaction of anti-F antibodies with anti-core antibodies, a specific enzyme-linked immunosorbent assay was performed for anti-core antibodies. The specificity of anti-F antibodies was confirmed using an F synthetic peptide. The prevalence of anti-F antibodies did not correlate with HCV RNA serum level, genotype, or stage of liver disease. Sequence analysis from 8 anti-F-positive and 5 anti-F-negative serum samples did not reveal any particular difference potentially accounting for their respective anti-F responses. In conclusion, the F protein elicits specific antibodies in 62% of individuals chronically infected with HCV; such anti-F response does not seem to be affected by the F sequence heterogeneity.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Proteínas do Core Viral/genética , Proteínas do Core Viral/imunologia , Adulto , Idoso , Epitopos , Feminino , Mutação da Fase de Leitura , Genótipo , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Estudos Soroepidemiológicos
10.
J Gen Virol ; 85(Pt 9): 2515-2523, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15302945

RESUMO

Previous work on hepatitis C virus (HCV) led to the discovery of a new form of virus particle associating virus and lipoprotein elements. These hybrid particles (LVP for lipo-viro-particles) are enriched in triglycerides and contain at least apolipoprotein B (apoB), HCV RNA and core protein. These findings suggest that LVP synthesis could occur in liver and intestine, the two main organs specialized in the production of apoB-containing lipoprotein. To identify the site of LVP production, the genetic diversity and phylogenetic relationship of HCV quasispecies from purified LVP, whole serum and liver biopsies from chronically infected patients were studied. HCV quasispecies from LVP and liver differed significantly, suggesting that LVP were not predominantly synthesized in the liver but might also originate in the intestine. The authors therefore searched for the presence of HCV in the small intestine. Paraffin-embedded intestinal biopsies from 10 chronically HCV-infected patients and from 12 HCV RNA-negative controls (10 anti-HCV antibody-negative and two anti-HCV antibody-positive patients) were tested for HCV protein expression. HCV NS3 and NS5A proteins were stained in small intestine epithelial cells in four of the 10 chronically infected patients, and not in controls. Cells expressing HCV proteins were apoB-producing enterocytes but not mucus-secreting cells. These data indicate that the small intestine can be infected by HCV, and identify this organ as a potential reservoir and replication site. This further emphasizes the interaction between lipoprotein metabolism and HCV, and offers new insights into hepatitis C infection and pathophysiology.


Assuntos
Hepatite C Crônica/metabolismo , Intestino Delgado/virologia , Proteínas não Estruturais Virais/metabolismo , Adulto , Apolipoproteínas B/metabolismo , Biópsia , Células Epiteliais/virologia , Variação Genética , Genoma Viral , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Humanos , Imuno-Histoquímica , Intestino Delgado/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Proteínas de Membrana/sangue , Dados de Sequência Molecular , Filogenia , Proteínas do Envelope Viral/análise , Proteínas do Envelope Viral/genética , Carga Viral , Proteínas não Estruturais Virais/análise
11.
BMC Immunol ; 3: 15, 2002 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-12398794

RESUMO

BACKGROUND: Macrophages, osteoclasts, dendritic cells, and microglia are highly specialized cells that belong to the mononuclear phagocyte system. Functional and phenotypic heterogeneity within the mononuclear phagocyte system may reveal differentiation plasticity of a common progenitor, but developmental pathways leading to such diversity are still unclear. RESULTS: Mouse bone marrow cells were expanded in vitro in the presence of Flt3-ligand (FL), yielding high numbers of non-adherent cells exhibiting immature monocyte characteristics. Cells expanded for 6 days, 8 days, or 11 days (day 6-FL, day 8-FL, and day 11-FL cells, respectively) exhibited constitutive potential towards macrophage differentiation. In contrast, they showed time-dependent potential towards osteoclast, dendritic, and microglia differentiation that was detected in day 6-, day 8-, and day 11-FL cells, in response to M-CSF and receptor activator of NFkappaB ligand (RANKL), granulocyte-macrophage colony stimulating-factor (GM-CSF) and tumor necrosis factor-alpha (TNFalpha), and glial cell-conditioned medium (GCCM), respectively. Analysis of cell proliferation using the vital dye CFSE revealed homogenous growth in FL-stimulated cultures of bone marrow cells, demonstrating that changes in differential potential did not result from sequential outgrowth of specific precursors. CONCLUSIONS: We propose that macrophages, osteoclasts, dendritic cells, and microglia may arise from expansion of common progenitors undergoing sequential differentiation commitment. This study also emphasizes differentiation plasticity within the mononuclear phagocyte system. Furthermore, selective massive cell production, as shown here, would greatly facilitate investigation of the clinical potential of dendritic cells and microglia.


Assuntos
Células Dendríticas/fisiologia , Macrófagos/fisiologia , Microglia/fisiologia , Osteoclastos/fisiologia , Proteínas Proto-Oncogênicas/biossíntese , Receptores Proteína Tirosina Quinases/biossíntese , Células-Tronco/fisiologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Proteínas de Transporte/farmacologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Células Dendríticas/citologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Glicoproteínas de Membrana/farmacologia , Proteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Osteoclastos/citologia , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Tirosina Quinase 3 Semelhante a fms
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA