Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Immunol ; 195(6): 2612-23, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26238491

RESUMO

Cellular FLIP (c-FLIP) specifically inhibits caspase-8 and suppresses death receptor-induced apoptosis. c-FLIP has also been reported to transmit activation signals. In this study, we report a novel function of c-FLIP involving inhibition of myeloid cell activation through antagonizing the selective innate signaling pathway. We found that conditional knockout of c-FLIP in dendritic cells (DCs) led to neutrophilia and splenomegaly. Peripheral DC populations, including CD11b(+) conventional DCs (cDCs), CD8(+) cDCs, and plasmacytoid DCs, were not affected by c-FLIP deficiency. We also found that c-FLIP knockout cDCs, plasmacytoid DCs, and bone marrow-derived DCs (BMDCs) displayed enhanced production of TNF-α, IL-2, or G-CSF in response to stimulation of TLR4, TLR2, and dectin-1. Consistent with the ability of c-FLIP to inhibit the activation of p38 MAPK, the enhanced activation of c-FLIP-deficient BMDCs could be partly linked to an elevated activation of p38 MAPK after engagement of innate receptors. Increased activation was also found in c-FLIP(+/-) macrophages. Additionally, the increased activation in c-FLIP-deficient DCs was independent of caspase-8. Our results reveal a novel inhibitory role of c-FLIP in myeloid cell activation and demonstrate the unexpected anti-inflammatory activity of c-FLIP. Additionally, our observations suggest that cancer therapy targeting c-FLIP downregulation may facilitate DC activation and increase T cell immunity.


Assuntos
Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/imunologia , Caspase 8/imunologia , Células Dendríticas/imunologia , Células Mieloides/imunologia , Animais , Anti-Inflamatórios , Apresentação de Antígeno/imunologia , Apoptose/imunologia , Antígeno B7-1/biossíntese , Antígeno B7-2/biossíntese , Células da Medula Óssea/imunologia , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Caspase 8/genética , Ativação Enzimática/genética , Ativação Enzimática/imunologia , Fator Estimulador de Colônias de Granulócitos/biossíntese , Antígenos de Histocompatibilidade Classe II/biossíntese , Inflamação/imunologia , Interleucina-2/biossíntese , Lectinas Tipo C/imunologia , Contagem de Leucócitos , Camundongos , Camundongos Knockout , Células Mieloides/citologia , Neutrófilos/citologia , Neutrófilos/imunologia , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais/imunologia , Esplenomegalia/imunologia , Linfócitos T/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
2.
Adv Mater ; 36(32): e2405065, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838331

RESUMO

Epitaxial growth of thin-film heterostructures is generally considered the most successful procedure to obtain interfaces of excellent structural and electronic quality between 3D materials. However, these interfaces can only join material systems with crystal lattices of matching symmetries and lattice constants. This article presents a novel category of interfaces, the fabrication of which is membrane-based and does not require epitaxial growth. These interfaces therefore overcome the limitations imposed by epitaxy. Leveraging the additional degrees of freedom gained, atomically clean interfaces are demonstrated between threefold symmetric sapphire and fourfold symmetric SrTiO3. Atomic-resolution imaging reveals structurally well-defined interfaces with a novel moiré-type reconstruction.

3.
Adv Mater ; 35(10): e2210989, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36585838

RESUMO

The exploration of crystalline nanostructures enhances the understanding of quantum phenomena occurring in spatially confined quantum matter and may lead to functional materials with unforeseen applications. A novel route to fabricating nanocrystalline oxide structures of exceptional quality is presented. This is achieved by utilizing a self-assembly process of ultrathin membranes composed of the desired oxide. The thermally induced self-assembly of nanocrystalline structures is driven by dewetting the oxide membranes once they are lifted off and transferred onto sapphire surfaces. In three successive steps, the process provides nanovoids, nanowires, and nanocrystals. Regardless of substrate orientation, the nanostructures are highly anisotropic in shape due to material retraction favoring low-index crystalline lattice directions of the membranes. The orientation of the nanostructures is provided precisely by the crystal lattice of the transferred membrane. The microstructure of the nanocrystals exhibits exceptional quality, characterized by a pristine crystal structure and uniform stoichiometry, both maintained all the way down to the well-developed crystalline facets. The demonstrated self-assembly process holds the potential to improve the understanding of surface diffusion phenomena at the interface of materials, which is important for advancing epitaxial growth technology and paves the way to fabricating crystalline nanostructures by the transfer and self-assembly of membranes.

4.
Nat Commun ; 6: 6353, 2015 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-25695215

RESUMO

Application of regulatory T cells (Tregs) in transplantation, autoimmunity and allergy has been extensively explored, but how Foxp3 and Treg stability is regulated in vivo is incompletely understood. Here, we identify a requirement for Deltex1 (DTX1), a contributor to T-cell anergy and Foxp3 protein level maintenance in vivo. Dtx1(-/-) Tregs are as effective as WT Tregs in the inhibition of CD4(+)CD25(-) T-cell activation in vitro. However, the suppressive ability of Dtx1(-/-) Tregs is greatly impaired in vivo. We find that Foxp3 expression is diminished when Dtx1(-/-) Tregs are co-transferred with effector T cells in vivo. DTX1 promotes the degradation of HIF-1α. Knockout of HIF-1α restores the Foxp3 stability and rescues the defective suppressive activity in Dtx1(-/-) Treg cells in vivo. Our results suggest that DTX1 exerts another level of control on Treg stability in vivo by sustaining the expression of Foxp3 protein in Tregs.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Hipersensibilidade/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linfócitos T Reguladores/fisiologia , Animais , Feminino , Doenças Inflamatórias Intestinais/imunologia , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ubiquitina-Proteína Ligases
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA