Role of CLA+T lymphocytes in the mechanisms triggering psoriasis

[eng] Psoriasis is a common immune-mediated inflammatory skin condition affecting around 2% of the population worldwide. Different disease subtypes have been described regarding their specific clinical phenotype: chronic plaques, inverse, guttate, pustular and erythrodermic. Disease onset occurs from a complex interaction between the immune system (mostly T cells) and environmental factors (like microbes), along with a susceptible genetic background, resulting in increased secretion of cytokines, governed by the IL-17/IL-23 axis, that enhance the inflammatory loop leading to the appearance of cutaneous lesions. The skin, besides being an effective physical barrier that protects us from external agents, accommodates diverse types of immune cells. Importantly, the extravasation of T cells from blood to cutaneous tissue is tightly regulated by the expression of specific adhesion molecules and their ligands on both T cells and dermal blood vessels respectively. The Cutaneous Lymphocyte-associated Antigen (CLA) identifies the subset of effector memory T cells with cutaneous tropism. CLA-expressing cells represent more than 90% of skin infiltrating T cells but, since these cells are able to recirculate between blood and tissue, a proportion of them can be found in circulation, thus being a useful tool with translational value for the study of T cell-mediated skin conditions. Our group has developed an ex vivo model of psoriasis based on the coculture of circulating CLA+ T cells with autologous epidermal cells obtained from lesional biopsies in the same patient. In this thesis, this model is used to discuss how circulating CLA+ T cells respond to relevant disease triggers such as microorganisms (Streptococcus pyogenes and Candida albicans) and lesional pro-inflammatory cytokines (IL-15 and IL-23) in plaque and guttate forms of psoriasis, as well as the association between cytokine response to microbes in vitro and patients exposure to the same microorganism, measured by the presence of specific antibodies in plasma. First, the study of S. pyogenes (SE)-specific antibodies revealed increased IgA response in both plaque and guttate psoriasis compared to healthy controls and atopic dermatitis patients. Interestingly, increased anti-SE IgA levels were reported in patients despite no history of streptococcal infection. Of note, anti-SE IgA levels positively correlated with CLA+ T cell dependent IL-17 response in vitro. Next, humoral response against C. Albicans (CA) was assessed and plaque psoriasis patients showed increased anti-CA IgA and IgG compared with guttate psoriasis and controls. T cell cytokines induced after stimulation with CA were evaluated in supernatants revealing raised Th17 and Th9 responses in psoriasis, specifically in the CLA+ T cell subset. Interestingly, anti-CA IgA levels and IL-17F/A responses were directly associated in CLA+ and CLA- T cells cocultures from plaque psoriasis only. Because patients with increased anti-CA IgA may carry pathological peculiarities, a broad proteomic profile was evaluated in plasma samples of plaque psoriasis patients reporting raised presence of proteins associated to anti-microbial humoral response that could link psoriasis and periodontitis. Finally, the influence of lesional pro-inflammatory cytokines IL-15 and IL-23 was examined in our model and revealed the synergistic induction of IL-17F and IL-17A cytokines by CLA+ T cells in cocultures from psoriasis but not healthy controls. This synergy required the presence of autologous epidermal cells, although it did not depend on skin-resident memory T cells, and was mainly mediated by activated CD4+ CLA+ T cells. In summary, this work has characterized novel mechanisms related to triggering factors of psoriasis and confirms that the subset of skin-tropic CLA+ memory T cells particularly are key inducers of IL-17 cytokines upon activation by these triggers, which may contribute to the feedforward inflammatory loop and perpetuate psoriasis pathogenesis

Analysis of Research Topics and Scientific Collaborations in Energy Saving Using Bibliometric Techniques and Community Detection

Concern about everything related to energy is increasingly latent in the world and therefore the use of energy saving concepts has been increasing over the past several years. The interest in the subject has allowed a conceptual evolution in the scientific community regarding the understanding of the adequate use of energy. The objective of this work is to determine the contribution made by international institutions to the specialized publications in the area of energy-saving from 1939 to 2018, using Scopus Database API Interface. The methodology followed in this research was to perform a bibliometric analysis of the whole scientific production indexed in Scopus. The world’s scientific production has been analysed in the following domains: First the trend over time, types of publications and countries, second, the main subjects and keywords, third, main institutions and their main topics, and fourth, the main journals and proceedings that publish on this topic. Then, these data are presented using community detection algorithms and graph visualization software. With these techniques, it is possible to determine the main areas of research activity as well as to identify the structures of the collaboration network in the field of renewable energy. The results of the work show that the literature in this field have substantially increased during the last 10 years

SEB-induced IL-13 production in CLA+ memory T cells defines Th2 high and Th2 low responders in atopic dermatitis

Atopic dermatitis; Cutaneous lymphocyte antigen; Skin infectionsDermatitis atópica; Antígeno cutáneo de linfocitos; Infecciones de la pielDermatitis atòpica; Antigen limfòcit cutani; Infeccions de la pellStaphylococcus aureus, memory skin-homing cutaneous lymphocyte-associated antigen (CLA)+ T cells and IL-13 constitute relevant play-ers in atopic dermatitis (AD) pathogenesis.1 Since circulating CLA+ T cells reflect cutaneous abnormalities present in human inflammatory skin diseases,2 an ex vivo coculture model made of purified circu-lating CLA+/− effector and central memory T cells and autologous lesional epidermal cells was established. We show a CLA-dependent production of IL-13 upon activation with staphylococcal enterotoxin B (SEB) that allows the differentiation of the Th2 high and Th2 low groups, with distinct clinical correlations between both groups, within a clinically homogeneous population of adult non-treated moderate-to- severe AD patients

Human CLA+ memory T cell and cytokines in psoriasis

Psoriasis is a common inflammatory skin condition resulting from the interplay between epidermal keratinocytes and immunological cellular components. This sustained inflammation is essentially driven by pro-inflammatory cytokines with the IL-23/IL-17 axis playing a critical central role, as proved by the clinical efficacy of their blockade in patients. Among all the CD45R0+ memory T cell subsets, those with special tropism for cutaneous tissues are identified by the expression of the Cutaneous Lymphocyte-associated Antigen (CLA) carbohydrate on their surface, that is induced during T cell maturation particularly in the skin-draining lymph nodes. Because of their ability to recirculate between the skin and blood, circulating CLA+ memory T cells reflect the immune abnormalities found in different human cutaneous conditions, such as psoriasis. Based on this premise, studying the effect of different environmental microbial triggers and psoriatic lesional cytokines on CLA+ memory T cells, in the presence of autologous epidermal cells from patients, revealed important IL-17 cytokines responses that are likely to enhance the pro-inflammatory loop underlying the development of psoriatic lesions. The goal of this mini-review is to present latest data regarding cytokines implicated in plaque and guttate psoriasis immunopathogenesis from the prism of CLA+ memory T cells, that are specifically related to the cutaneous immune system

Small-scale variation of vegetation in a mixed forest understorey is partly controlled by the effect of overstory composition on litter accumulation

We investigated how richness and composition of vascular plant species in the understory of a mixed hardwood forest stand varied with respect to the abundance and composition of the overstory. The stand is in central Spain and represents the southernmost range of distribution of several tree and herbaceous species in Europe. Understory species were identified in 46 quadrats (0.25 m2) where variables litter depth and light availability were measured. In addition, we estimated tree density, basal area, and percent basal area by tree species within 6-m-radius areas around each plot. Species richness and composition were studied using path analysis and scale-dependent geostatistical methods, respectively. We found that the relative abundance of certain trees species in the overstory was more important than total overstory abundance in explaining understory species richness. Richness decreased as soil litter depth increased, and soil litter increased as the relative proportion of Fagus sylvatica in the overstory increased, which accounted for a negative, indirect effect of Fagus sylvatica on richness. Regarding understory species composition, we found that some species distributed preferentially below certain tree species. For example, Melica uniflora was most frequent below Fagus sylvatica and Quercus petraea while the increasing proportion of Q. pyrenaica in the overstory favored the presence of Cruciata glabra, Arenaria montana, Prunus avium, Conopodium bourgaei, Holcus mollis, Stellaria media and Galium aparine in the understory. Overall, these results emphasize the importance of individual tree species in controlling the assemblage and richness of understory species in mixed stands. We conclude that soil litter accumulation is one way through which overstory composition shapes the understory community

Medication Non-Adherence in Rheumatology, Oncology and Cardiology: A Review of the Literature of Risk Factors and Potential Interventions

Medication adherence is directly associated with health outcomes. Adherence has been reviewed extensively; however, most studies provide a narrow scope of the problem, covering a specific disease or treatment. This project’s objective was to identify risk factors for non-adherence in the fields of rheumatology, oncology, and cardiology as well as potential interventions to improve adherence and their association with the risk factors. The project was developed in three phases and carried out by a Steering Committee made up of experts from the fields of rheumatology, oncology, cardiology, general medicine, and hospital and community pharmacy. In phase 1, a bibliographic review was performed, and the articles/reviews were classified according to the authors’ level of confidence in the results and their clinical relevance. In phase 2, 20 risk factors for non-adherence were identified from these articles/reviews and agreed upon in Steering Committee meetings. In phase 3, potential interventions for improving adherence were also identified and agreed upon. The results obtained show that adherence is a dynamic concept that can change throughout the course of the disease, the treatments, and other factors. Educational interventions are the most studied ones and have the highest level of confidence in the authors’ opinion. Information and education are essential to improve adherence in all patients

Planetary boundary layer and Saharan air layer top height determination using ceilometer and micro pulse lidar. Intercomparison for two case studies

Comunicación presentada en: 2012 European Aerosol Conference (EAC-2012), B-WG01S2P30, celebrada del 2 al 7 de septiembre de 2012 en Granada

Non invasive exploration of a late republican fortified settlement in the mid Tagus valley. The site of Cerro de la Breña (Talaván, Cáceres)

En este trabajo se muestran los primeros resultados de una exploración del asentamiento fortificado del Cerro de la Breña (Talaván, Cáceres), principalmente mediante la combinación de una batería de sistemas de registro no invasivos (prospección geomagnética, georradar, tomografía eléctrica y LiDAR). Los resultados acreditan la existencia de un complejo sistema defensivo, que encerraría una trama urbana densa y regular. Estos datos son valorados a la luz del conocimiento previo que existía sobre el sitio, para así poder avanzar una lectura en términos históricos del sentido de este asentamiento. Este marco se define como un proceso de transformación de la estructura territorial del valle medio del Tajo (actual Alta Extremadura) a caballo entre el final de la Edad del Hierro y los primeros momentos de la dominación romana. Se valora en este sentido el contexto geográfico y la evidencia disponible sobre otros sitios arqueológicos del entorno. La propuesta de interpretación se orienta a considerar al Cerro de la Breña como un asentamiento directamente vinculado con la implantación romana entre finales del siglo II e inicios del siglo I a.C.This paper shows the first results of an exploration of the fortified settlement of Cerro de la Breña (Talaván, Cáceres), mainly through the combination of non-invasive methods (geomagnetic survey, GPR, electric tomography and Li- DAR). The results prove the existence of a complex defensive system, which would enclose a dense and regular urban layout. These data are valued in light of the previous knowledge about the site, in order to advance an interpretative proposal in functional and historical terms about this settlement. This framework is the process of transformation of the territorial structure of the middle Tagus valley (now Alta Extremadura) between the end of the Iron Age and the first moments of Roman domination. In this sense, the geographical context and the available evidence on other archaeological sites in the area are valued. The interpretation is oriented to consider Cerro de la Breña as a settlement directly linked to the Roman implantation between the end of the 2nd century and the beginning of the 1st century BC

Proyecto «Capacidad Profesional Docente en Extremadura» (CPDEx), una nueva visión de los Centros educativos extremeños

El Proyecto CPDEx es una nueva estrategia para mejora la respuesta educativa que los Centros extremeños ofrecen a su alumnado. Se trata de mejorar la educación fortaleciendo la profesión, a partir de la integración de las competencias personales del profesorado, las competencias institucionales de los Centros, y el modo en que los Centros gestionan el conocimiento profesional y la cultura escolar

The use of interactive response systems as a tool to favor proactive learning in Engineering

El desarrollo de las tecnologías de la información y la comunicación (TIC) ha permitido el surgimiento de herramientas didácticas en el campo de la educación, proporcionando herramientas prácticas para apoyar a las clases presenciales. En este contexto, los sistemas electrónicos de respuesta estudiantil pueden ser útiles para introducir un elemento tecnológico motivador en las lecciones, así como una nueva metodología. En este estudio, además del uso de los sistemas de respuesta interactiva o clickers, se ha introducido la tecnología de aprendizaje móvil mediante la elaboración de una metodología de uso de las herramientas Kahoot y Telegram en la asignatura "Fundamentos Físicos en la Ingeniería II" del Grado en Ingeniería Electrónica Industrial. El Departamento de Física Aplicada de la Universidad de Córdoba tiene una amplia experiencia en el uso de Clickers en clases teóricas con grupos grandes para diferentes grados universitarios, pero ahora el uso de tecnologías móviles de aprendizaje se ha introducido en grupos de tamaño medio para clases prácticas. Usando esta nueva metodología, los estudiantes de grupos medianos realizan un cuestionario durante la lección de resolución de problemas, donde utilizaron sus conocimientos adquiridos durante la clase. La realización del cuestionario permite a los profesores evaluar en tiempo real el nivel del estudiante y utilizar la retroalimentación para abordar los problemas iniciales y los malentendidos. Los resultados muestran que los sistemas de respuesta interactiva son altamente valorados por los estudiantes, que lo perciben como una herramienta para mejorar el aprendizaje y aumentar la competencia en el aula.The development of information and communication technologies (ICT) has enabled the emergence of teaching tools in the education field, providing practical tools to support face-to-face classes. In this context, electronic student response systems can be useful for introducing a motivating technological element into the lessons, as well as a new methodology. In this study, in addition to the use of interactive response systems or clickers, mobile learning technology has been introduced by developing a methodology for using the Kahoot and Telegram tools in the subject “Physical Foundations of Engineering II” of Electronic Engineering Degree. Department of Applied Physics of University of Cordoba has a broad experience using Clickers in theory classes with large groups for different university degrees, but now the use of mobile learning technologies has been introduced in medium-sized groups for practical classes. Using this new methodology, students of medium-sized groups perform a quiz during the problem solving lesson, where they utilized their knowledge gained during the class. The completion of the quiz allows teachers to assess the student’s level in real time, and to use the feedback to address initial problems and misunderstandings. Results show the interactive response systems are highly valued by students, who perceive it as a tool to improve learning and increase competition in the classroom