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1.
J Dairy Sci ; 102(7): 6210-6225, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030924

RESUMO

Cow milk and dairy products have a good nutritional value that could be improved by increasing the concentrations of several compounds such as carotenoids and liposoluble vitamins A and E. Their concentrations in milk are dependent on their respective dietary intakes, but the transfer from feeds to milk seems to be limited by dietary, digestive, or metabolic factors linked to lipids that could differ between dairy breeds. The effect of dietary fat supplement (provided as extruded linseed) on carotenoid, vitamin E, and vitamin A status as well as their transfer from diet to milk were explored in mid-lactating dairy cows (Holstein or Montbéliarde breed) receiving either corn silage or hay as the main forage. Carotenoid and tocopherol status were higher in cows fed hay than in those fed corn silage, both at the plasma and milk level. The transfer rate for carotenoids was the same regardless of forage, whereas the transfer rate for tocopherols was greater (1.71 vs. 1.20%, respectively) for cows fed hay compared with corn silage. Cows fed extruded linseed had greater plasma concentrations of tocopherols (+25%) compared with those that did not, regardless of forage, but linseed treatment only changed xanthophyll (+35%) concentrations. This would suggest that the lipid supplement increased the availability of xanthophylls and tocopherols for the cows. However, carotenoid transfer into milk remained low and unaffected by the lipid supplement, whatever the forage nature, suggesting a limiting unknown process. Carotenoid status was marginally different between breeds because plasma concentrations were higher in Montbéliarde cows besides lower intakes. In milk, 13-E-ß-carotene concentration was also higher for Montbéliarde cows because of a 2-fold higher transfer rate than for Holstein cows. In contrast, Holstein cows had higher transfer rates of α-tocopherol and vitamin A activity, linked to higher milk fat yield. For the first time, this study proposed an evaluation of the transfer rate of lipid micronutrients from diet to milk in cows. The study highlighted that these compounds follow distinct patterns of regulation during their transfer. However, in these experimental conditions, it was not possible to show that a dietary fat supplement could increase the concentration of these compounds in milk fat.


Assuntos
Carotenoides/análise , Bovinos/metabolismo , Dieta/veterinária , Gorduras na Dieta/administração & dosagem , Linho , Vitaminas/análise , Animais , Carotenoides/sangue , Suplementos Nutricionais , Digestão , Feminino , Lactação/fisiologia , Óleo de Semente do Linho/administração & dosagem , Lipídeos , Micronutrientes , Leite/química , Sementes , Silagem , Vitamina A/análise , Vitamina A/sangue , Vitamina E/análise , Vitamina E/sangue , Vitaminas/sangue , Zea mays
2.
J Autoimmun ; 99: 73-80, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30745186

RESUMO

OBJECTIVES: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients. METHODS: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cytometry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by immunohistochemistry. This study prospectively included 44 adult patients with biopsy-proven IgAV and 24 age- and sex-matched healthy controls. RESULTS: We observed reduced proportions of circulating CXCR5-and CXCR3-expressing memory CD4 T cells at diagnosis but normal values at remission. The plasma levels of Th1-related cytokines (IL-12, IL-27 and IFNγ) and of the TFH-related cytokine, IL-21, were paradoxically not reduced in patients. We observed increased plasma concentrations of the CXCR5 ligand, CXCL13, and of the CXCR3 ligands, CXCL10/11, suggesting a potential relocation of the corresponding T cells into inflamed tissues. We then confirmed the recruitment of CXCR3-expressing T cells into the skin and kidneys. In the skin, T-cell infiltrates mainly co-localized with damaged dermal small vessels. Finally, patients with the largest kidney T-cell infiltrates were also those with the highest proteinuria. CONCLUSION: Altogether, our results strongly suggest that, in IgAV patients, CXCL10/11 orchestrate the recruitment of CXCR3-expressing T cells in injured tissues, contributing to tissue damage and disease activity.

3.
J Dairy Sci ; 102(2): 1131-1143, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30591341

RESUMO

Although the effects of cow diet on cheese sensory properties have been well documented, the putative interactions between the biochemical and microbial milk components and their respective roles in the development of the sensory properties of cheeses have yet to be explored in depth. The aim of this study was to evaluate the specific contribution of milk fat composition to the formation of cheese sensory properties. Two creams with different fat compositions were obtained from cows fed either pasture or maize silage. Cheeses were manufactured from the same skim milk (identical chemical and microbial composition) with either the pasture- or maize silage-origin pasteurized cream added. The gross composition and microbial composition of milks did not vary with cream origin. In milks and cheeses, the fatty acid (FA) profiles were modified by the origin of the cream. The concentrations of C18:0 and unsaturated FA such as cis-9 C18:1, trans-11 C18:1, C18:3n-3, total conjugated linoleic acids, and mono- and polyunsaturated FA were higher in milks and cheeses with the pasture-origin cream than in those with the maize-origin cream. In contrast, the maize milks and cheeses had higher concentrations of short- and medium-chain saturated FA, C16:0, and C18:2n-6. The level of lipolysis was 11% in the cheese rind and only 0.30% in the cheese core. The rind of pasture cheeses had a higher concentration of free C18:0 and C18:3n-3 and a lower concentration of free C14:0 and free C16:0 than the rind of maize cheeses. The levels of major microbial groups were similar in pasture and maize cheeses at different stages of ripening. The pasture cheeses had a more elastic and creamier texture, a yellower color, and a thinner rind than the maize cheeses, but the odor and aroma of cheeses were not affected by the origin of the cream, despite a few modifications in the balance of volatile compounds from FA catabolism. Based on these results, we conclude that milk fat composition modulated by cow diet had a direct role in the texture of the cheese but no effect on flavor. The high degree of lipolysis in cheese rind, along with the higher concentration of long-chain unsaturated free FA in pasture cheeses may be responsible for antimicrobial activity, which could explain differences in the appearance of cheese rind.


Assuntos
Queijo/análise , Gorduras/análise , Leite/química , Paladar , Animais , Bovinos , Dieta/veterinária , Ácidos Graxos/análise , Ácidos Graxos Insaturados/análise , Feminino , Aromatizantes/análise , Ácidos Linoleicos Conjugados/análise , Lipólise , Leite/microbiologia , Odorantes , Sensação , Silagem , Zea mays
4.
Sci Rep ; 8(1): 200, 2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29317671

RESUMO

The objectives of this study were to explore bacterial community assembly from cow teat skin to raw milk cheeses and to evaluate the role of farming systems on this assembly using 16S rRNA gene high-throughput sequencing. The two grazing systems studied (extensive vs. semi-extensive) had a greater effect on the microbiota of cow teat skin than on that of raw milks and cheeses. On teat skin, the relative abundance of several taxa at different taxonomic levels (Coriobacteriia, Bifidobacteriales, Corynebacteriales, Lachnospiraceae, Atopobium, and Clostridium) varied depending on the grazing system and the period (early or late summer). In cheese, the abundance of sub-dominant lactic acid bacteria (LAB) varied depending on the grazing system. Overall, 85% of OTUs detected in raw milks and 27% of OTUs detected in ripened cheeses were also found on cow teat skin. Several shared OTUs were assigned to taxa known to be involved in the development of cheese sensory characteristics, such as Micrococcales, Staphylococcaceae, and LAB. Our results highlight the key role of cow teat skin as a reservoir of microbial diversity for raw milk, and for the first time, that cow teat skin serves as a potential source of microorganisms found in raw-milk cheeses.


Assuntos
Bovinos/microbiologia , Queijo/microbiologia , Herbivoria , Glândulas Mamárias Animais/microbiologia , Microbiota , Animais , Bovinos/fisiologia , Queijo/normas , Feminino , Lactobacillales/isolamento & purificação , Estações do Ano
5.
Nat Commun ; 9(1): 68, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29302034

RESUMO

Despite being implicated in non-lymphoid tissues, non-recirculating T cells may also exist in secondary lymphoid organs (SLO). However, a detailed characterization of this lymphoid-resident T cell pool has not yet been done. Here we show that a substantial proportion of CD4 regulatory (Treg) and memory (Tmem) cells establish long-term residence in the SLOs of specific pathogen-free mice. Of these SLOs, only T cell residence within Peyer's patches is affected by microbiota. Resident CD4 Treg and CD4 Tmem cells from lymph nodes and non-lymphoid tissues share many phenotypic and functional characteristics. The percentage of resident T cells in SLOs increases considerably with age, with S1PR1 downregulation possibly contributing to this altered homeostasis. Our results thus show that T cell residence is not only a hallmark of non-lymphoid tissues, but can be extended to secondary lymphoid organs.


Assuntos
Envelhecimento/imunologia , Vida Livre de Germes , Memória Imunológica , Tecido Linfoide/imunologia , Linfócitos T Reguladores , Animais , Feminino , Camundongos Endogâmicos C57BL , Microbiota , Receptores de Lisoesfingolipídeo/metabolismo , Linfócitos T Reguladores/metabolismo
6.
Elife ; 62017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-29239722

RESUMO

Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on calcineurin activation. Accordingly, in vivo calcineurin inhibition leads the most self-reactive naive CD4 T cells to adopt the phenotype of their less self-reactive cell-counterparts. Collectively, our findings demonstrate that calcium-mediated activation of the calcineurin pathway acts as a rheostat to shape both the phenotype and effector potential of naive CD4 T cells in the steady-state.


Assuntos
Cálcio/metabolismo , Diferenciação Celular , Fenótipo , Linfócitos T Reguladores/fisiologia , Animais , Calcineurina/metabolismo , Células Cultivadas , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais
7.
J Immunol ; 199(6): 1998-2007, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28779024

RESUMO

So far, peripheral T cells have mostly been described to circulate between blood, secondary lymphoid organs (SLOs), and lymph in the steady state. This nomadic existence would allow them to accomplish their surveying task for both foreign Ags and survival signals. Although it is now well established that γδ T cells can be rapidly recruited to inflammatory sites or in certain tumor microenvironments, the trafficking properties of peripheral γδ T cells have been poorly studied in the steady state. In the present study, we highlight the existence of resident γδ T cells in the SLOs of specific pathogen-free mice. Indeed, using several experimental approaches such as the injection of integrin-neutralizing Abs that inhibit the entry of circulating lymphocytes into lymph nodes and long-term parabiosis experiments, we have found that, contrary to Ly-6C-/+CD44lo and Ly-6C+CD44hi γδ T cells, a significant proportion of Ly-6C-CD44hi γδ T cells are trapped for long periods of time within lymph nodes and the spleen in the steady state. Specific in vivo cell depletion strategies have allowed us to demonstrate that macrophages are the main actors involved in this long-term retention of Ly-6C-CD44hi γδ T cells in SLOs.


Assuntos
Linfonodos/imunologia , Macrófagos/imunologia , Baço/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Animais , Antígenos Ly/metabolismo , Comunicação Celular , Movimento Celular , Células Cultivadas , Receptores de Hialuronatos/metabolismo , Imunidade Inata , Vigilância Imunológica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo
8.
Int J Biometeorol ; 61(8): 1371-1379, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28154992

RESUMO

This study was undertaken to first quantify the effect of heat stress on milk yield and components of Tarentaise in comparison to Holstein cows. A dataset of 16,143 monthly individual records of production traits was collected for 435 Tarentaise and 543 Holstein cows from 21 farms in Tunisia (2009 to 2014). This dataset was merged with meteorological data from 5 public stations relative to the 21 farms. The temperature-humidity index (THI), calculated as a combination of ambient temperature and relative humidity, was used to characterize heat stress. When the THI increased from an average value of 53.7 in winter to 75.4 in summer, the Holstein and Tarentaise cows decreased their milk production by 0.93 and 0.15 kg/day, respectively. Milk fat, protein, and urea content decreased similarly in both breeds (-2.20 g/kg, -1.40 g/kg, and -14 mg/L, respectively), and the milk somatic cell count increased for Holstein cows (+352,000/mL) while decreased for Tarentaise cows (-160,000/mL). The second aim of this study was to describe the relationship between the variations of the milk yields between the summer and the winter (Δ milk yields) and some barn characteristics during the hot season. A survey carried out on 19 of the 21 previous farms permitted to conclude that the closed buildings led to a higher decrease in milk yield between the summer and winter than the open buildings (-1.13 vs. -0.27 kg/day). A metallic roof had a more negative impact on Δ milk yields than the other roof types (-1.04 vs. -0.15 kg/day).


Assuntos
Doenças dos Bovinos/fisiopatologia , Transtornos de Estresse por Calor/fisiopatologia , Transtornos de Estresse por Calor/veterinária , Lactação , Leite/química , Animais , Bovinos , Clima , Gorduras/análise , Feminino , Abrigo para Animais , Umidade , Região do Mediterrâneo , Proteínas do Leite/análise , Temperatura Ambiente , Ureia/análise
9.
Colloids Surf B Biointerfaces ; 149: 312-321, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27780088

RESUMO

A quartz crystal microbalance (QCM) was constructed to assess if such a biosensor has value as a complementary real-time label-free analysis platform for the biopharmaceutical industry. This was achieved through modifying QCM crystals with a low-fouling carboxymethyl-dextran layer bearing Protein A, and then injecting solutions containing Etanercept (i.e., Enbrel®) into the QCM chambers. The kinetics of Enbrel® - Protein A interactions was modeled using the Langmuir binding model and Enbrel® concentrations between 0.75-300ngmL-1. The resulting equilibrium dissociation and association constants (KD and KA) were 5.06×10-8M and 1.98×107M-1, respectively. The association and dissociation rate constants (kon and koff) decreased substantially as Enbrel® concentration, [C], increased, despite that the net binding rate, (kon[C]+koff), increased. The decrease in kon and koff was hypothesized to be a consequence of mass transport limitations. To verify this, QCM dissipation measurements were analyzed to provide insight on solution viscosity. As Enbrel® concentration increased, the net change in dissipation, ΔD, became larger. An augmentation of ΔD is associated with a higher solution viscosity, which would result in an increase in mass transport limitations. Therefore, the decrease in kon and koff for increasing Enbrel® concentration can be attributed to mass transport limitations. In conclusion, QCM is a valuable complementary real-time label-free biosensor analysis platform for the biopharmaceutical industry. Unlike the surface plasmon resonance (SPR) platform, QCM allows measuring dissipation, which can provide insight on how mass transport limitations impact interaction kinetics.


Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Técnicas Biossensoriais , Dextranos/química , Etanercepte/isolamento & purificação , Técnicas de Microbalança de Cristal de Quartzo/instrumentação , Proteína Estafilocócica A/química , Adsorção , Anti-Inflamatórios não Esteroides/química , Indústria Farmacêutica , Etanercepte/química , Humanos , Cinética , Peso Molecular , Ligação Proteica , Soluções , Viscosidade
10.
Genet Sel Evol ; 48(1): 89, 2016 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-27852216

RESUMO

BACKGROUND: Volatile organic compounds determine important quality traits in cheese. The aim of this work was to infer genetic parameters of the profile of volatile compounds in cheese as revealed by direct-injection mass spectrometry of the headspace gas from model cheeses that were produced from milk samples from individual cows. METHODS: A total of 1075 model cheeses were produced using raw whole-milk samples that were collected from individual Brown Swiss cows. Single spectrometry peaks and a combination of these peaks obtained by principal component analysis (PCA) were analysed. Using a Bayesian approach, we estimated genetic parameters for 240 individual spectrometry peaks and for the first ten principal components (PC) extracted from them. RESULTS: Our results show that there is some genetic variability in the volatile compound fingerprint of these model cheeses. Most peaks were characterized by a substantial heritability and for about one quarter of the peaks, heritability (up to 21.6%) was higher than that of the best PC. Intra-herd heritability of the PC ranged from 3.6 to 10.2% and was similar to heritabilities estimated for milk fat, specific fatty acids, somatic cell count and some coagulation parameters in the same population. We also calculated phenotypic correlations between PC (around zero as expected), the corresponding genetic correlations (from -0.79 to 0.86) and correlations between herds and sampling-processing dates (from -0.88 to 0.66), which confirmed that there is a relationship between cheese flavour and the dairy system in which cows are reared. CONCLUSIONS: This work reveals the existence of a link between the cow's genetic background and the profile of volatile compounds in cheese. Analysis of the relationships between the volatile organic compound (VOC) content and the sensory characteristics of cheese as perceived by the consumer, and of the genetic basis of these relationships could generate new knowledge that would open up the possibility of controlling and improving the sensory properties of cheese through genetic selection of cows. More detailed investigations are necessary to connect VOC with the sensory properties of cheese and gain a better understanding of the significance of these new phenotypes.


Assuntos
Queijo/análise , Espectrometria de Massas/métodos , Prótons , Paladar/genética , Animais , Bovinos , Padrões de Herança/genética , Leite/química , Fenótipo , Análise de Componente Principal , Compostos Orgânicos Voláteis/análise
11.
J Immunol ; 195(4): 1449-58, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26123353

RESUMO

To better apprehend γ/δ T cell biological functions in the periphery, it appears crucial to identify markers highlighting the existence of distinct phenotypic and functional γ/δ T cell subsets. Interestingly, the expression of CD44 and Ly-6C subdivides murine peripheral γ/δ T cells into several subsets, with Ly-6C(-) CD44(hi) γ/δ T cells corresponding to the IL-17-producing CD27(-) γ/δ T cell subset exhibiting innate-like features. By comparing the other subsets to naive and memory CD8(+) α/ß T cells, in this study, we show that Ly-6C(- or +) CD44(lo) and Ly-6C(+)CD44(hi) γ/δ T cells greatly resemble, and behave like, their CD8(+) α/ß T cell counterparts. First, like memory CD8(+) α/ß T cells, Ly-6C(+)CD44(hi) γ/δ T cells are sparse in the thymus but largely increased in proportion in tissues. Second, similarly to naive CD8 α/ß T cells, CD44(lo) γ/δ T cells are poorly cycling in vivo in the steady state, and their proportion declines with age in secondary lymphoid organs. Third, CD44(lo) γ/δ T cells undergo spontaneous proliferation and convert to a memory-like Ly-6C(+)CD44(hi) phenotype in response to lymphopenia. Finally, CD44(lo) γ/δ T cells have an intrinsic high plasticity as, upon appropriate stimulation, they are capable of differentiating nonetheless into Th17-like and Th1-like cells but also into fully functional Foxp3(+) induced regulatory T cell-like γ/δ T cells. Thus, peripheral CD27(+) γ/δ T cells, commonly considered as a functionally related T cell compartment, actually share many common features with adaptive α/ß T cells, as both lineages include naive-like and memory-like lymphocytes with distinct phenotypic, functional, and homeostatic characteristics.


Assuntos
Imunidade Adaptativa , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Antígenos Ly/genética , Antígenos Ly/metabolismo , Expressão Gênica , Homeostase , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Imunofenotipagem , Interleucina-17/biossíntese , Linfopenia/imunologia , Linfopenia/metabolismo , Camundongos , Camundongos Knockout , Fenótipo , Transdução de Sinais , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral
12.
J Immunol ; 195(4): 1791-803, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26170390

RESUMO

An uncontrolled exaggerated Th17 response can drive the onset of autoimmune and inflammatory diseases. In this study, we show that, in T cells, Foxo1 is a negative regulator of the Th17 program. Using mixed bone marrow chimeras and Foxo1-deficient mice, we demonstrate that this control is effective in vivo, as well as in vitro during differentiation assays of naive T cells with specific inhibitor of Foxo1 or inhibitors of the PI3K/Akt pathway acting upstream of Foxo1. Consistently, expressing this transcription factor in T cells strongly decreases Th17 generation in vitro as well as transcription of both IL-17A and IL-23R RORγt-target genes. Finally, at the molecular level, we demonstrate that Foxo1 forms a complex with RORγt via its DNA binding domain to inhibit RORγt activity. We conclude that Foxo1 is a direct antagonist of the RORγt-Th17 program acting in a T cell-intrinsic manner.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Subpopulações de Linfócitos T/metabolismo , Células Th17/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/deficiência , Fatores de Transcrição Forkhead/genética , Humanos , Imunofenotipagem , Interleucina-17/genética , Interleucina-17/metabolismo , Contagem de Linfócitos , Camundongos , Camundongos Knockout , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/química , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas , Domínios e Motivos de Interação entre Proteínas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Células Th17/citologia , Células Th17/imunologia , Transcrição Genética
13.
J Immunol ; 193(12): 5914-23, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25381435

RESUMO

CD4 regulatory T cells (Tregs) can be subdivided into two subsets according to Ly-6C expression in the periphery. Phenotypic analysis, imaging, and adoptive-transfer experiments of peripheral Ly-6C(-) and Ly-6C(+) Tregs reveal that the nonexpression of Ly-6C by ∼70% of peripheral Tregs depends on TCR signaling events. Interestingly, Ly-6C(-) Tregs express higher surface amounts of key immunosuppressive molecules than do Ly-6C(+) Tregs and produce constitutively anti-inflammatory cytokines. In line with their phenotype, Ly-6C(+) Tregs exhibit poor suppressive capacities in vitro and in vivo. Finally, although Ly-6C(-) Tregs maintain their numbers with age, Ly-6C(+) Tregs gradually disappear. Altogether, our data strongly suggest that both the survival and suppressive functions of peripheral CD4 Tregs rely on their ability to receive strong TCR signals.


Assuntos
Imunomodulação , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fatores Etários , Envelhecimento/imunologia , Animais , Antígenos Ly/genética , Antígenos Ly/metabolismo , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Expressão Gênica , Imunofenotipagem , Linfonodos/imunologia , Linfonodos/metabolismo , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Transgênicos , Fenótipo
14.
Nat Commun ; 4: 2209, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23900386

RESUMO

Upon activation, naive CD4 T cells differentiate into a variety of T-helper-cell subsets characterized by different cytokine production and functions. Currently, lineage commitment is considered to depend mostly on the environmental context to which naive CD4 T cells are exposed. Here we challenge this model based on the supposed homogeneity of the naive CD4 T-cell compartment. We show that peripheral naive CD4 T cells can be subdivided into two subsets according to Ly-6C expression. Furthermore, the two newly defined subsets (Ly-6C(-) and Ly-6C(+) naive CD4 T cells) are not equal in their intrinsic ability to commit into the induced regulatory T-cell lineage. Finally, phenotypic analysis, imaging and adoptive transfer experiments reveal that Ly-6C expression is modulated by self-recognition, allowing the dichotomization of the naive CD4 T-cell compartment into two cell subsets with distinct self-reactivity. Altogether, our results show that naive CD4 T cells with the highest avidity for self are prone to differentiate into regulatory T cells.


Assuntos
Diferenciação Celular/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Antígenos Ly/metabolismo , Polaridade Celular/imunologia , Citometria de Fluxo , Fluorescência , Fatores de Transcrição Forkhead/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células Th17/citologia , Células Th17/imunologia
15.
Proc Natl Acad Sci U S A ; 110(32): 13085-90, 2013 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-23878221

RESUMO

The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma [mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice)]. In this model, cancer cells disseminate early but remain dormant for several weeks. Then, MT/ret mice develop cutaneous metastases and, finally, distant metastases. A total of 35% of MT/ret mice develop a vitiligo, a skin depigmentation attributable to the lysis of normal melanocytes, associated with a delay in tumor progression. Here, we find that regulatory CD4(+) T cells accumulate in the skin, the spleen, and tumor-draining lymph nodes of MT/ret mice not developing vitiligo. Regulatory T-cell depletion and IL-10 neutralization led to increased occurrence of vitiligo that correlated with a decreased incidence of melanoma metastases. In contrast, inflammatory monocytes/dendritic cells accumulate in the skin of MT/ret mice with active vitiligo. Moreover, they inhibit tumor cell proliferation in vitro through a reactive oxygen species-dependent mechanism, and both their depletion and reactive oxygen species neutralization in vivo increased tumor cell dissemination. Altogether, our data suggest that regulatory CD4(+) T cells favor tumor progression, in part, by inhibiting recruitment and/or differentiation of inflammatory monocytes in the skin.


Assuntos
Inflamação/imunologia , Melanoma/imunologia , Monócitos/imunologia , Linfócitos T Reguladores/imunologia , Animais , Proliferação de Células , Feminino , Citometria de Fluxo , Humanos , Inflamação/genética , Inflamação/patologia , Linfonodos/imunologia , Linfonodos/metabolismo , Linfonodos/patologia , Masculino , Melanoma/genética , Melanoma/patologia , Metalotioneína/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Monócitos/metabolismo , Metástase Neoplásica , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/imunologia , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Pele/imunologia , Pele/metabolismo , Pele/patologia , Baço/imunologia , Baço/metabolismo , Linfócitos T Reguladores/metabolismo , Fatores de Tempo , Vitiligo/genética , Vitiligo/imunologia
16.
J Acoust Soc Am ; 132(5): 3138-47, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23145599

RESUMO

A hybrid model describing the acoustic properties of plates with macroperforations that can be unevenly distributed on the plate surface and backed by woven or precision woven meshes with microscopic perforations is proposed. The plate perforations may be of circular or rectangular shapes. Since the perforated plate may not necessarily be considered as an equivalent fluid, its impedance is calculated by the Maa model [Noise Control Eng. J. 29, 77-84 (1987)], whereas the Johnson-Champoux-Allard model [J. Appl. Phys. 70, 1975-1979 (1991)] is used for the mesh, considered as an equivalent fluid. A simple model for the elementary cell of the mesh structure is proposed in order to calculate parameters that can be considered as the thermal characteristic length Λ' and the viscous characteristic length Λ. An effective airflow resistivity is introduced to account for the increase of particle velocity through the mesh placed behind the carrying macroperforated plate and is used in the transfer matrix approach to obtain the impedance of the whole multilayer system. The hybrid model seems to represent a good approach of this multilayer system. The theoretical predictions are compared with experimental measurements.


Assuntos
Acústica/instrumentação , Som , Desenho de Equipamento , Modelos Teóricos , Movimento (Física) , Porosidade , Temperatura Ambiente , Fatores de Tempo , Viscosidade
17.
J Immunol ; 189(7): 3339-46, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22933631

RESUMO

Work over the last decades has led to the identification of the factors that influence the survival and homeostasis of conventional T cells. IL-7 and TCR signaling promote the survival of naive CD4(+) and CD8(+) T cells in lymphoreplete mice and their proliferation in a lymphopenic environment, whereas survival and homeostatic proliferation of memory CD4(+) and CD8(+) T cells crucially depend on a combination of IL-7 and IL-15. In contrast, there is little information regarding the factors driving the proliferation of regulatory CD4(+) T cells in response to lymphopenia. In this study, we investigated whether regulatory CD4(+) T cell proliferation in response to lymphopenia was guided by classical homeostatic resources, such as IL-2, IL-7, or TCR-MHC interactions. Altogether, our data suggest that, although homeostatic proliferation of conventional naive CD4(+) T cells is closely related to IL-7 levels, the proliferation of regulatory CD4(+) T cells in response to lymphopenia appears to be primarily controlled by IL-2. The capacity of IL-7 to augment conventional T cell proliferation with minimal concomitant regulatory T cell expansion may be clinically exploitable in the treatment of patients with lymphopenia, especially in the case of chronic viral diseases or cancer immunotherapy.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Compartimento Celular/imunologia , Homeostase/imunologia , Interleucina-2/fisiologia , Interleucina-7/fisiologia , Animais , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/transplante , Compartimento Celular/genética , Ciclo Celular/genética , Ciclo Celular/imunologia , Proliferação de Células , Células Cultivadas , Genes Reporter , Homeostase/genética , Linfopenia/genética , Linfopenia/imunologia , Linfopenia/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
18.
J Opt Soc Am A Opt Image Sci Vis ; 29(3): 367-73, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22472768

RESUMO

This paper deals with a full vectorial generalization of the aperiodic Fourier modal method (AFMM) in cylindrical coordinates. The goal is to predict some key characteristics such as the bending losses of waveguides having an arbitrary distribution of the transverse refractive index. After a description of the method, we compare the results of the cylindrical coordinates AFMM with simulations by the finite-difference time-domain (FDTD) method performed on an S-bend structure made by a 500 nm × 200 nm silicon core (n=3.48) in silica (n=1.44) at a wavelength λ=1550 nm, the bending radius varying from 0.5 up to 2 µm. The FDTD and AFMM results show differences comparable to the variations obtained by changing the parameters of the FDTD simulations.

19.
Int J Food Sci Nutr ; 62(6): 660-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21591986

RESUMO

The present study investigated the effect of the consumption of two cheese varieties differing for fat quality on blood lipid profile and redox status biomarkers in 30 selected healthy volunteers, consuming either the experimental cheese (from milk produced by cows fed a grass and maize silage based diet with 5% of linseed oil added) or the control cheese (from normal cows' milk) for 4 weeks according to a crossover design. The experimental cheese had a lower content of medium-chain saturated fatty acids and a higher content of stearic acid and polyunsaturated fatty acids; its consumption led to higher levels of vitamins C and E and stearic acid in blood, while myristic acid and oxidized low-density lipoprotein concentrations were significantly lower. As myristic acid and oxidized low-density lipoprotein are highly correlated with increased atherogenic risk and vitamins C and E with antioxidant activity, the enrichment of cows' diet with linseed oil could provide a dietary option to prevent cardiovascular diseases risk.


Assuntos
Antioxidantes/metabolismo , Queijo , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/farmacologia , Alimentos Fortificados , Óleo de Semente do Linho/farmacologia , Lipídeos/sangue , Adulto , Animais , Ácido Ascórbico/sangue , Biomarcadores/sangue , Bovinos , Estudos Cross-Over , Dieta/veterinária , Método Duplo-Cego , Ácidos Graxos/análise , Feminino , Linho/química , Humanos , Lipoproteínas LDL/sangue , Masculino , Ácido Mirístico/sangue , Oxirredução , Projetos Piloto , Valores de Referência , Silagem , Ácidos Esteáricos/sangue , Vitamina E/sangue , Adulto Jovem
20.
J Agric Food Chem ; 59(9): 4947-54, 2011 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-21434695

RESUMO

The effect of animal feeding on milk volatile organic compounds (VOCs) of metabolic origin was tested on a hay-based diet (H), a highly diversified pasture under continuous grazing (CG), or a less diversified pasture under rotational grazing (RG). Individual milk of 24 Montbéliarde cows (8 per treatment) were sampled after 2 weeks. Pasture-derived milk was richer (p < 0.05) in camphene, sabinene, ß-caryophyllene, and skatole than H milk. Neither milk yield nor fat content affected the majority of VOCs measured. Skatole increased slightly with milk yield, while indole and cineole decreased slightly with milk fat content but with poor regression (R(2) < 0.54). Multivariate analysis showed that, on the basis of those VOCs of metabolic origin whose concentration differed between treatment (dimethyl-sulfone, skatole, toluene, undecanoic acid, 1-octadecene, benzeneacetaldehyde, octanoic acid, and 2-pentanone-4-hydroxy-4-methyl), it was possible to obtain good discriminations among feeding systems. This study is promising for a future use of VOCs of metabolic origin to trace animal feeding systems.


Assuntos
Ração Animal/análise , Criação de Animais Domésticos/métodos , Bovinos/metabolismo , Leite/química , Compostos Orgânicos Voláteis/análise , Animais , Feminino , Leite/metabolismo , Compostos Orgânicos Voláteis/metabolismo
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