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By stabilizing the evaporation dynamics of a microliter fluorocarbon droplet, we demonstrate a fast-scan optofluidic Fourier transform (FT) spectrometer on the tip of an optical fiber operating in the 1000-2000â nm window with a resolution of 3.5â cm-1 (i.e., <1â nm at 1560â nm). Compared with other FT near-infrared (NIR) small-scale spectrometers reported in the literature, the fluorocarbon droplet spectrometer shows the largest wavelength span and span/resolution ratio, allowing spectral analysis of broadband or narrowband radiation to be easily performed. Our results open the way for the practical application of droplet spectrometers as advanced optofluidic NIR analyzers with small size and low cost that are capable of operating in harsh environments, even in the absence of electrical power sources.
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Refractometría , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A droplet optical resonator is a unique environment to investigate light-matter interaction and optomechanics in liquids. Here, we report on light pressure effects derived from whispering gallery modes excited in a liquid-polymer droplet micro-resonator by free-space laser scattering. From the nonlinear resonance spectrum observed in the visible, we provide evidence of photon pressure exerted at the liquid-air boundary and quantify it with a coherent physical model. Our findings pave the way to studies on micro-rheology and nonlinear optofluidics, where droplets serve as miniature liquid laboratories.
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PURPOSE: To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. METHODS: The TDr method requires two static scans per subject: one early (~ 0-10 min after the injection) and one late (typically 50-70 min or 90-100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical-cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. RESULTS: TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. CONCLUSIONS: TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.
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Enfermedad de Alzheimer , Amiloidosis , Enfermedad de Alzheimer/diagnóstico por imagen , Amiloide/metabolismo , Compuestos de Anilina , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Humanos , Cinética , Tomografía de Emisión de PositronesRESUMEN
As molecular spectroscopy makes its comeback to the limelight of fundamental sciences, scientists need ever better coherent light sources and diagnostic methods. Of particular importance for molecular spectroscopy is the mid infrared spectral region, where strong and narrow ro-vibrational excitations have their fundamental transition frequencies. Unfortunately, much technology in some portions of this spectral region is still rather pioneering. Here we present a high-resolution spectroscopy experiment, based on a molecular beam setup, which pushes the measured linewidth close to the transit time limit, on the order of 100 kHz. Moreover, we discuss the issue of frequency-noise characterization and the linewidth measurement of the ultrastable infrared laser used in the experiment.
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Background and Aim: The availability of new treatments for metastatic castrate-resistant prostate cancer (mCRPC) patients increases the need for reliable biomarkers to help clinicians to choose the better sequence strategy. The aim of the present retrospective and observational work is to investigate the prognostic value of 18F-fluorocholine (18F-FCH) positron emission tomography (PET) parameters in mCRPC. Materials and Methods: Between March 2013 and August 2016, 29 patients with mCRPC were included. They all received three-weekly docetaxel after androgen deprivation therapy, and they underwent 18F-FCH PET/computed tomography (CT) before and after the therapy. Semi-quantitative indices such as maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) with partial volume effect (PVC-SUV) correction, metabolically active tumour volume (MATV), and total lesion activity (TLA) with partial volume effect (PVC-TLA) correction were measured both in pre-treatment and post-treatment 18F-FCH PET/CT scans for each lesion. Whole-body indices were calculated as sum of values measured for each lesion (SSUVmax, SPVC-SUV, SMATV, and STLA). Progression-free survival (PFS) and overall survival (OS) were considered as clinical endpoints. Univariate and multivariate hazard ratios for whole-body 18F-FCH PET indices were performed, and p < 0.05 was considered as significant. Results: Cox regression analysis showed a statistically significant correlation between PFS, SMATV, and STLA. No correlations between OS and 18F-FCH PET parameters were defined probably due to the small sample size. Conclusions: Semi-quantitative indices such as SMATV and STLA at baseline have a prognostic role in patients treated with docetaxel for mCRPC, suggesting a potential role of 18F-FCH PET/CT imaging in clinical decision-making.
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Colina/análogos & derivados , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Cintigrafía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/administración & dosificación , Colina/administración & dosificación , Colina/química , Docetaxel/administración & dosificación , Docetaxel/química , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Metástasis de la Neoplasia , Pronóstico , Supervivencia sin Progresión , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/patología , Carga Tumoral/efectos de los fármacosRESUMEN
High-resolution spectroscopy in the 1-10 µm region has never been fully tackled for the lack of widely-tunable and practical light sources. Indeed, all solutions proposed thus far suffer from at least one of three issues: they are feasible only in a narrow spectral range; the power available for spectroscopy is limited; the frequency accuracy is poor. Here, we present a setup for high-resolution spectroscopy, whose approach can be applied in the whole 1-10 µm range. It combines the power of quantum cascade lasers (QCLs) and the accuracy achievable by difference frequency generation using an orientation patterned GaP crystal. The frequency is measured against a primary frequency standard using the Italian metrological fibre link network. We demonstrate the performance of the setup by measuring a vibrational transition in a highly-excited metastable state of CO around 6 µm with 11 digits of precision.
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The anatomy of the soft parts of Ilyocypris ramirezi Cusminsky & Whatley, 1996 is described and illustrated for the first time, based on findings of this species from water bodies in the shallow areas of the Llancanelo basin, south-west of Mendoza Province, Argentina. This species is common in Quaternary and extant environments of the Pampa and Patagonian regions. Its distribution is now extending in Argentina to the Central-West area, locally named "Cuyo region". Ilyocypris ramirezi is a good environmental indicator and constitutes a useful tool in paleolimnological studies.
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Crustáceos/clasificación , Distribución Animal , Estructuras Animales/anatomía & histología , Estructuras Animales/crecimiento & desarrollo , Animales , Argentina , Tamaño Corporal , Crustáceos/anatomía & histología , Crustáceos/crecimiento & desarrollo , Femenino , Masculino , Tamaño de los Órganos , América del SurRESUMEN
PURPOSE: The aim of this study was to assess in healthy subjects the safety, tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an oral selective sphingosine-1-phosphate receptor 1 (S1P1) modulator in development for multiple sclerosis, by using an uptitration scheme up to supratherapeutic doses. METHODS: This was a double-blind, placebo-controlled, randomised, parallel group, uptitration study. Male and female subjects received ascending oral doses of ponesimod (n=12) or placebo (n=4) once daily for 3 days at each dose level (10-20-40-60-80-100mg). RESULTS: The most frequent adverse events were chest discomfort, headache, dizziness, dyspnoea, abdominal pain, and night sweats. Chest discomfort and dyspnoea were considered dose-limiting. A transient decrease in heart rate was observed following the first 10-mg ponesimod dose (maximum mean decrease of 9 beats per minute (bpm) (placebo: 2 bpm)). After uptitration, effects on heart rate were indistinguishable from placebo. A dose-dependent effect on pulmonary function tests was observed and reached a plateau with 60-80 mg ponesimod (maximum mean decrease from baseline of 1.24l (-30.5%) in forced expiratory volume in 1s). A plateau in mean lymphocyte count reduction of approximately 70% from baseline was reached at the 40 mg dose level. Observed effects were fully reversible within 10days after treatment discontinuation. No relevant sex differences were observed. CONCLUSIONS: At supratherapeutic doses, symptoms of chest discomfort and dyspnoea were dose-limiting. An uptitration dosing scheme is to be preferred in clinical studies in patients in order to limit effects of ponesimod on heart rate and atrioventricular (AV) conduction.
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Receptores de Lisoesfingolípidos/metabolismo , Tiazoles/efectos adversos , Tiazoles/farmacología , Adolescente , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiazoles/administración & dosificación , Adulto JovenAsunto(s)
Antihipertensivos/uso terapéutico , Dermatosis del Pie/tratamiento farmacológico , Hipertensión Pulmonar/tratamiento farmacológico , Fenilpropionatos/uso terapéutico , Piridazinas/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , Úlcera Cutánea/tratamiento farmacológico , Anciano , Dermatosis del Pie/etiología , Humanos , Hipertensión Pulmonar/etiología , Masculino , Esclerodermia Sistémica/complicaciones , Úlcera Cutánea/etiología , Resultado del TratamientoRESUMEN
In this work we developed a Monte Carlo (MC) model of the Sedecal Argus pre-clinical PET scanner, using GATE (Geant4 Application for Tomographic Emission). This is a dual-ring scanner which features DOI compensation by means of two layers of detector crystals (LYSO and GSO). Geometry of detectors and sources, pulses readout and selection of coincidence events were modeled with GATE, while a separate code was developed in order to emulate the processing of digitized data (for example, customized time windows and data flow saturation), the final binning of the lines of response and to reproduce the data output format of the scanner's acquisition software. Validation of the model was performed by modeling several phantoms used in experimental measurements, in order to compare the results of the simulations. Spatial resolution, sensitivity, scatter fraction, count rates and NECR were tested. Moreover, the NEMA NU-4 phantom was modeled in order to check for the image quality yielded by the model. Noise, contrast of cold and hot regions and recovery coefficient were calculated and compared using images of the NEMA phantom acquired with our scanner. The energy spectrum of coincidence events due to the small amount of (176)Lu in LYSO crystals, which was suitably included in our model, was also compared with experimental measurements. Spatial resolution, sensitivity and scatter fraction showed an agreement within 7%. Comparison of the count rates curves resulted satisfactory, being the values within the uncertainties, in the range of activities practically used in research scans. Analysis of the NEMA phantom images also showed a good agreement between simulated and acquired data, within 9% for all the tested parameters. This work shows that basic MC modeling of this kind of system is possible using GATE as a base platform; extension through suitably written customized code allows for an adequate level of accuracy in the results. Our careful validation against experimental data confirms that the developed simulation setup is a useful tool for a wide range of research applications.
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Tomografía de Emisión de Positrones/instrumentación , Tomografía de Emisión de Positrones/veterinaria , Animales , Ratones , Método de Montecarlo , Fantasmas de Imagen/veterinaria , Ratas , Tomografía Computarizada de Emisión/instrumentación , Tomografía Computarizada de Emisión/veterinariaRESUMEN
BACKGROUND: The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study aimed to examine the predictive role of frailty on long-term mortality in elderly subjects with CHF. MATERIALS AND METHODS: The study assessed long-term mortality after 12-year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a 'Frailty Staging System'. RESULTS: Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75.9 +/- 6.7); subjects without CHF were prevalently female (56.4%) and younger than 75 years (mean 74.0 +/- 6.3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70.0% to 94.4%, P < 0.03) than in those without (43.8.% to 88.3%, P < 0.0001) CHF. The Kaplan-Meier analysis shows that at 9 years the probability of survival progressively decreased as frailty increased (45.5% to 0%) in subjects with CHF and from 62.8% to 25.9% in subjects without CHF. The Cox regression analysis indicated that frailty is predictive of mortality in the multivariate model adjusted for several variables including sex and age in subjects with and without CHF. Moreover, the analysis showed that frailty is more predictive of mortality in elderly subjects with CHF when it was analyzed either as continuous (1.48 vs. 1.36) or as a dummy (3 vs. 1 = 1.62 vs. 1.24) variable. CONCLUSIONS: Thus mortality among elderly subjects with or without CHF increases with frailty. Moreover, frailty is more predictive of long-term mortality in elderly subjects with than in those without CHF. Hence, frailty represents a new independent variable for predicting long-term mortality in elderly subjects with CHF.
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Anciano Frágil , Insuficiencia Cardíaca/mortalidad , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Indicadores de Salud , Humanos , Italia , Masculino , Análisis Multivariante , Análisis de SupervivenciaAsunto(s)
Quimiocinas/fisiología , Neumonía/inmunología , Receptores de Quimiocina/fisiología , Linfocitos T/inmunología , Humanos , Leucocitos/fisiología , Pulmón/irrigación sanguínea , Enfermedades Pulmonares/inmunología , Activación de Linfocitos , Neumonía/tratamiento farmacológico , Linfocitos T Colaboradores-Inductores/fisiologíaRESUMEN
Chemokines dictate regional trafficking of functionally distinct T cell subsets. In rodents and humans, a unique subset of CD4(+)CD25(+) cytotoxic T lymphocyte antigen (CTLA)-4(+) regulatory T cells (Treg) has been proposed to control peripheral tolerance. However, the molecular basis of immune suppression and the trafficking properties of Treg cells are still unknown. Here, we determined the chemotactic response profile and chemokine receptor expression of human blood-borne CD4(+)CD25(+) Treg cells. These Treg cells were found to vigorously respond to several inflammatory and lymphoid chemokines. Treg cells specifically express the chemokine receptors CCR4 and CCR8 and represent a major subset of circulating CD4(+) T cells responding to the chemokines macrophage-derived chemokine (MDC)/CCL22, thymus and activation-regulated chemokine (TARC)/CCL17, I-309/CCL1, and to the virokine vMIP-I (ligands of CCR4 and CCR8). Blood-borne CD4(+) T cells that migrate in response to CCL1 and CCL22 exhibit a reduced alloproliferative response, dependent on the increased frequency of Treg cells in the migrated population. Importantly, mature dendritic cells preferentially attract Treg cells among circulating CD4(+) T cells, by secretion of CCR4 ligands CCL17 and CCL22. Overall, these results suggest that CCR4 and/or CCR8 may guide Treg cells to sites of antigen presentation in secondary lymphoid tissues and inflamed areas to attenuate T cell activation.
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Linfocitos T CD4-Positivos/fisiología , Quimiocinas CC/metabolismo , Quimiotaxis/fisiología , Inmunoconjugados , Receptores de Quimiocina/biosíntesis , Receptores de Interleucina-2 , Abatacept , Antígenos CD , Antígenos de Diferenciación , Biomarcadores , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/metabolismo , Antígeno CTLA-4 , Células Cultivadas , Quimiocina CCL1 , Quimiocina CCL17 , Quimiocina CCL19 , Quimiocina CCL20 , Quimiocina CCL22 , Quimiocina CXCL11 , Quimiocinas CC/farmacología , Quimiocinas CXC/metabolismo , Quimiocinas CXC/farmacología , Humanos , Proteínas Inflamatorias de Macrófagos/metabolismo , Proteínas Inflamatorias de Macrófagos/farmacología , Receptores CCR4 , Receptores CCR6 , Receptores CCR8RESUMEN
Fractalkine (FKN, CX3CL1) is a membrane-bound CX3C chemokine induced by primary proinflammatory signals in vascular endothelial cells (ECs). Here we examined the role of FKN in polarized Th1 or Th2 responses. Proinflammatory signals, including LPS, IL-1, TNF, and CD40 ligand, induced FKN, as did IFN-gamma, which had synergistic activity with TNF. IL-4 and IL-13 did not stimulate the expression of FKN and markedly reduced induction by TNF and IFN-gamma. TNF alone or combined with IFN-gamma also induced release of soluble FKN, which was inhibited by IL-4 and IL-13. In light of this differential regulation of FKN by the master cytokines that control polarized responses, we analyzed the interaction of FKN with natural killer (NK) cells and polarized T-cell populations. NK cells expressed high levels of the FKN receptor CX3CR1 and responded to FKN. CX3CR1 was preferentially expressed in Th1 compared with Th2 cells. Th1 but not Th2 cells responded to FKN. By immunohistochemistry, FKN was expressed on ECs in psoriasis, a Th1-dominated skin disorder, but not in Th2-driven atopic dermatitis. Similarly, ECs in Mycobacterium tuberculosis granulomatous lymphadenitis, but not those in reactive lymph node hyperplasia or in Castelman's disease, showed immunoreactive FKN. These results indicate that regulated expression of FKN in ECs participates in an amplification circuit of polarized type I responses.
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Quimiocinas CX3C/biosíntesis , Endotelio Vascular/inmunología , Células Asesinas Naturales/inmunología , Proteínas de la Membrana/biosíntesis , Células TH1/inmunología , Adulto , Ligando de CD40/metabolismo , Receptor 1 de Quimiocinas CX3C , Enfermedad de Castleman/inmunología , Quimiocina CX3CL1 , Quimiotaxis de Leucocito , Dermatitis Atópica/inmunología , Endotelio Vascular/efectos de los fármacos , Humanos , Recién Nacido , Interferón gamma/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Linfadenitis/inmunología , Psoriasis/inmunología , Receptores de Citocinas/metabolismo , Receptores del VIH/metabolismo , Células Th2/inmunologíaRESUMEN
CD4(+) helper T type 1 (Th1) and Th2 cells are critical mediators of inflammatory diseases. Although T cells represent only a fraction of the leukocytes that are found in the lung during inflammation, they play a critical role in coordinating the immune response to infectious agents and allergens. T cells have the ability to rapidly expand in response to specific stimuli and to differentiate into effector cells that, through the production of soluble factors such as cytokines and chemokines, communicate with other cells to initiate a cascade of inflammatory events. The objective of this review is to outline the cellular and molecular mechanisms involved in the generation and recruitment of Th1 and Th2 cells in the lung. Defining these mechanisms should lead to improved immunopharmacological strategies for prophylaxis and therapy.
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Activación de Linfocitos/inmunología , Cooperación Linfocítica/inmunología , Hipersensibilidad Respiratoria/inmunología , Infecciones del Sistema Respiratorio/inmunología , Células TH1/inmunología , Células Th2/inmunología , Animales , Quimiocinas/fisiología , Citocinas/fisiología , Humanos , Pulmón/inmunologíaRESUMEN
Th1 and Th2 cells, which produce distinct sets of cytokines, differentially express several chemokine receptors that may regulate their tissue-specific localization. Although the expression pattern and regulation of chemokines are likely to play a critical role in many immunopathological processes, they remain largely unknown. Here, we investigated the requirements for Th1 and Th2 cells to produce the Th2 cell-attracting chemokines thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and I-309. TCR triggering of Th1 and Th2 cells leads to production of MDC and I-309 (CCR4 and CCR8 ligands, respectively), whereas TARC (CCR4 ligand) is selectively produced by Th2 cells. Secretion of these chemokines appears to be independent of endogenous production of IL-4 and IFN-gamma. IL-12 and IFN-alpha, cytokines that promote the differentiation of human Th1 cells, selectively inhibit secretion and mRNA expression of MDC and I-309 by Th1 cells. Suppression of I-309 secretion results in a decreased chemotactic effect on L1.2 cells transfected with human CCR8, indicating that IL-12 and IFN-alpha may inhibit the recruitment of CCR8-expressing cells such as Th2 cells. The inhibition of Th2 cell-attracting chemokines MDC and I-309 illustrates a novel mechanism by which IL-12 and IFN-alpha could promote and maintain an ongoing Th1 response.
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Quimiocinas CC/biosíntesis , Interferón-alfa/farmacología , Interleucina-12/farmacología , Receptores de Antígenos de Linfocitos T/inmunología , Células TH1/metabolismo , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos B/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular , Células Cultivadas , Quimiocina CCL1 , Quimiocina CCL17 , Quimiocina CCL22 , Quimiocinas CC/antagonistas & inhibidores , Quimiocinas CC/genética , Quimiocinas CC/metabolismo , Quimiotaxis de Leucocito/efectos de los fármacos , Quimiotaxis de Leucocito/inmunología , Relación Dosis-Respuesta a Droga , Humanos , Interferón-alfa/metabolismo , Interferón gamma/análisis , Interferón gamma/fisiología , Interleucina-12/metabolismo , Interleucina-4/análisis , Interleucina-4/fisiología , Ligandos , Activación de Linfocitos , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores CCR4 , Receptores CCR8 , Receptores de Quimiocina/genética , Receptores de Quimiocina/inmunología , Receptores de Quimiocina/metabolismo , Células TH1/citología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Células Th2/metabolismo , TransfecciónAsunto(s)
Inflamación/inmunología , Células TH1/inmunología , Células Th2/inmunología , Animales , Movimiento Celular , Homeostasis/inmunología , Humanos , Inmunidad , Integrinas/metabolismo , Receptores de Quimiocina/inmunología , Selectinas/metabolismo , Células TH1/metabolismo , Células Th2/metabolismoRESUMEN
Th1 and Th2 cells are functionally distinct subsets of CD4+ T lymphocytes whose tissue-specific homing to sites of inflammation is regulated in part by the differential expression of P- and E-selectin ligands and selected chemokine receptors. Here we investigated the expression and function of beta 1 integrins in Th1 and Th2 cells polarized in vitro. Th1 lymphocytes adhere transiently to the extracellular matrix ligands laminin 1 and fibronectin in response to chemokines such as RANTES and stromal cell-derived factor-1, and this process is paralleled by the activation of the Rac1 GTPase and by a rapid burst of actin polymerization. Selective inhibitors of phosphoinositide-3 kinase prevent efficiently all of the above processes, whereas the protein kinase C inhibitor bisindolylmaleimide prevents chemokine-induced adhesion without affecting Rac1 activation and actin polymerization. Notably, chemokine-induced adhesion to beta 1 integrin ligands is markedly reduced in Th2 cells. Such a defect cannot be explained by a reduced sensitivity to chemokine stimulation in this T cell subset, nor by a defective activation of the signaling cascade involving phosphoinositide-3 kinase, Rac1, and actin turnover, as all these processes are activated at comparable levels by chemokines in the two subsets. We propose that reduced beta 1 integrin-mediated adhesion in Th2 cells may restrain their ability to invade and/or reside in sites of chronic inflammation, which are characterized by thickening of basement membranes and extensive fibrosis, requiring efficient interaction with organized extracellular matrices.
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Quimiocina CCL5/fisiología , Quimiocinas CXC/fisiología , Integrina beta1/fisiología , Células Th2/inmunología , Regulación hacia Arriba/inmunología , Actinas/metabolismo , Biopolímeros/metabolismo , Antígenos CD18/biosíntesis , Calcio/metabolismo , Adhesión Celular/inmunología , Quimiocina CXCL12 , Proteínas de la Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Humanos , Integrina alfa6beta1 , Integrina beta1/biosíntesis , Integrinas/metabolismo , Líquido Intracelular/metabolismo , Laminina/metabolismo , Unión Proteica/inmunología , Receptores de Laminina/metabolismo , Transducción de Señal/inmunología , Células TH1/inmunología , Células TH1/metabolismo , Células Th2/metabolismoRESUMEN
During the past year significant advances have been made in our understanding of the factors contributing to the differentiation of CD4+ T helper cell subsets. These have been driven, in part, by the realization that cytokines from the innate immune response, such as interleukin-12 (IL-12) and interferons (IFNs), play a critical role in T cell subset differentiation. This review covers some of the most recent data concerning the divergent role that IFNs have in the differentiation of human versus mouse T helper cell subsets. In this review we discuss the molecular basis for the specie-specific effect of type I IFN on the selective induction of Th1 type immune responses. Furthermore, since IFN-beta is used in the treatment of multiple sclerosis (MS) we discuss the potential effects of such treatment and the value of the Th1/Th2 paradigm in MS.