Influence of exercise on NA- and Hsp72-induced release of IFNã by the peritoneal suspension of macrophages and lymphocytes from genetically obese Zucker rats

Regular physical exercise is recognized as a nonpharmacological therapeutic strategy in the treatment of metabolic syndrome, and has been proposed for improving obesity, diabetic status, insulin resistance, and immune response. The aim of the present study was to evaluate the effect of a regular exercise program (treadmill running, 5 days/week for 14 weeks at 35 cm/s for 35 min in the last month) on the release of the pro-inflammatory cytokine interferon gamma (IFNã) by peritoneal cells (macrophages and lymphocytes) from obese Zucker rats (fa/fa) in response to noradrenaline (NA) and heat shock proteins of 72 kDa (Hsp72), and the possible adaptation due to training for a bout acute exercise (a single session of 25–35 min at 35 cm/s). In healthy (lean Fa/fa) and obese animals, peritoneal cells released greater concentrations of IFNã in response to Hsp72 and lower concentrations in response to NA. The regular exercise training protocol, evaluated in the obese animals, produced a clear change in the regulation of the release of IFNã. Peritoneal immune cells from trained animals released more IFNã in response to NA, but there was a reduction in the release of IFNã in response to Hsp72. In the obese animals, regular exercise caused a change in the inhibitory effect of NA (which now becomes stimulatory) and the stimulatory effect of Hsp72e (which now becomes inhibitory) in relation to the release of IFNã. This reflects that Hsp72, induced by the prior release of NA following exercise-induced stress, plays a role in the homeostatic balance of release of IFNã by peritoneal immune cells in obese animals during exercise (AU)

Inmunología de la mucosa oral: Revisión / Immunology of oral mucosa: A review

Durante los últimos 50 años numerosas publicaciones han tratado de explicar los cambios inmunológicos en relación con exclusivas o determinadas enfermedades. El objetivo de esta presentación es realizar una revisión sobre lo publicado hasta el momento sobre la respuesta del sistema inmune innato y adaptativo en relación con la mucosa oral, un panorama sobre el rol o roles de las células inmunes, citoquinas, receptores, factores de crecimiento y otros productos secretorios y en los distintos elementos inmunológicos que actúan sobre la mucosa oral asociados con los estados de salud, inflamación, stress crónico, desregulación inmune, longevidad tolerancia inmune e inmunosenescencia (AU)

During the last 50 years several papers have been put forward to explain induce immunological changes in relationship with exclusive or determinate oral diseases. The objective of this presentation is to make a rewire about what is published at the moment about of innated and adaptive immune response, in relationship with oral mucosa, and an overwide of the role (s) of immune cells, cytoquines, receptors, grow factors, and other secretory products associated with health, inflammation, chronic stress, Immune dysregulation aging, inmuno tolerance and inmunosenescence (AU)

Adipose tissue lymphocytes: types and roles

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Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, ãäT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development (AU)

Terapias celulares en Oncología / Cell therapies in Oncology

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Roquin: a novel immune regulator that represses ICOS expression and differentiation of self-reactive T cells

La expresión controlada y coordinada de receptores coestimuladoresen células T es crítica para la generación de respuestasinmunológicas óptimas y, al mismo tiempo, el mantenimientode la autotolerancia. CD28 está expresado constitutivamenteen células T naive y es requerido para un «priming» efectivo delas células T. En cambio, la molécula Coestimuladora Inducible(ICOS), sólo augmenta su expresión después del “priming” de lascélulas T y es esencial durante la fase efectora de la respuesta delas células T colaboradoras. De acuerdo con estos diferentes roles,los ligandos de CD28 – B7.1/B7.2 - sólo augmentan su expresiónen células presentadoras de antígeno (APCs) en presencia deun estímulo inmunogénico. En cambio, el ligando de ICOS– B7h- está extensamente expresado en APCs. La caracterización recientede la cepa de ratón sanroque que contiene una mutación en elgen roquin ha sugerido que la alteración de la cinética de expresiónde ICOS puede tener efectos profundos en la tolerancia inmunológica,incluyendo la formación de autoanticuerpos y el desarrollode lupus y diabetes autoinmune. En el presente artículo discutimoslos mecanismos celulares y moleculares que podrían explicarcómo la regulación de ICOS por Roquin puede contribuir a larepresión de la autoinmunidad órgano-específica y sistémica

Controlled and coordinated expression of T cell costimulatoryreceptors is critical to elicit optimal immune responses whilemaintaining self tolerance. CD28 is constitutively expressed onnaïve T cells and required for effective T cell priming. Conversely,Inducible Costimulator (ICOS) is only upregulated after Tcell priming and is essential during the effector phase of the helperT cell response. Consistent with these different roles, CD28ligands – B7.1/B7.2 - are only upregulated on antigen-presentingcells (APCs) in the presence of immunogenic stimuli while ICOSligand – B7h - is widely expressed on APCs. The recent characterizationof the sanroque mouse strain harboring a mutation inthe roquin gene has suggested that altering the kinetics of ICOSexpression can exert profound effects on immunological toleranceincluding formation of autoantibodies and development oflupus and autoimmune diabetes. Here we discuss the cellular andmolecular mechanisms that may explain how Roquin’s regulationof ICOS can contribute to repress organ-specific and systemicautoimmunity

Synthetic particulate antigen delivery systems for vaccination

La encapsulación de un antígeno (proteína, péptido o DNA)en partículas sintéticas constituye un punto de partida razonablepara el diseño de vacunas subcelulares efectivas. Al dotarlo delas dimensiones de una partícula, se favorece su visualización porcélulas presentadoras de antígeno (APC), como las células dendríticas(DC). Utilizando distintos materiales y procedimientosde fabricación, la tecnología farmacéutica puede construir partículascon un amplio rango de tamaños y variadas propiedadesde superficie. Es nuestro objetivo con esta revisión analizar cómoestas propiedades físicas afectan a la intensidad y al tipo de respuestainmunitaria que producen. Así, partículas de distinto tamañopodrían poner en juego distintas APC y subtipos de DC. Susuperficie puede ser recubierta con ligandos que promueven laendocitosis receptor-específica y algún inmunoestimulante intrínsecoco-encapsulado junto con el antígeno dentro de la mismapartícula. El mecanismo de captura antigénica y el tipo de señalde activación pueden ser decisivos para potenciar y modular larespuesta inmunitaria al tipo deseado, Th2/humoral o Th1/citotoxica.Adicionalmente, las partículas que son de naturaleza poliméricapueden liberar lentamente el antígeno encapsulado, deforma continua o pulsátil, evitando la necesidad de administracionesrepetidas normalmente requerida para las vacunas tradicionales.Las partículas sintéticas para la encapsulación de antígenosconstituyen por tanto, una buena herramienta que puede hacerposible el diseño de vacunas seguras y efectivas con una sola administración,algunos de los atributos de una vacuna ideal. Existenciertos problemas tecnológicos, pero no parecen insalvables

Synthetic particles as carriers for antigens display a greatpotential and versatility for the design of effective vaccines. Supportedby multiple raw materials and preparation procedures,they can be engineered over a wide range of sizes, variable surfacenature and patterns of antigen release. It is our goal in thisreview to evaluate how these physical characteristics decide thetype of immune response the particles will develop, aiming at amore rational design of effective and safer synthetic subunit vaccines.So, as a function of their size, they will be uptaken by differentantigen presenting cell (APC) or dendritic cell (DC) subsets;certain ligands can be attached to the particle surfaces to promotereceptor-specific endocitosis and any immunopotentiatorco-encapsulated with the antigen in the same particle. The mechanismof antigen uptake and the signal for activating DC can bedecisive to increase and skew a Th1/cytotoxic or Th2/humoralresponse. Also, the antigen release rate has influence on the generationof immunological memory and an adequate profile of antigenrelease from these particles can mimic boosters of the traditionalvaccines.The current tendencies are oriented towards the developmentof new vaccines containing perfectly characterized antigens, establishedand safe, and with composition and preparation methodsrigorously controlled. The use of synthetic particles as vectorsmay be considered as adjuvants that accomplish with these requisites,being able to induce a response even at the mucosal level.There are technological handicaps faced by developers of syntheticparticles based vaccines but do not appear to be insurmountable