Les travaux présentés dans cette thèse s’intéressent à l’immobilisation de biomolécules pour le développement d’outils d’analyse multiparamétrique pour la caractérisation d’échantillons biologiques et le diagnostic, sur un support de type biopuce couplé à une détection colorimétrique.Un premier axe de recherche concerne le développement de tests d’hybridation d’acides nucléiques et d’immunotests à haut-débit automatisés sur plaque de filtration. Cette méthode a permis la mise au point d’un test de génotypage automatisé pour le dépistage transfusionnel haut-débit (génotypage érythrocytaire étendu) en collaboration avec l’Établissement Français du Sang Rhône-Alpes (EFS-RA). Il permet d’analyser 96 échantillons en quatre heures, et de caractériser six génotypes par échantillon. Cet outil a fait l’objet d’une validation sur un panel de 293 donneurs.La seconde partie des travaux présentés s’intéresse au développement d’un procédé d’immobilisation d’oligonucléotides sur un polymère particulier (PolyshrinkTM) pour l’élaboration d’un système d’analyse miniaturisé. Plusieurs stratégies d’activation ont été envisagées et ont abouti à la mise au point d’une technique d’immobilisation d’oligonucleotides in situ dans des plots d’hydrogel. La méthode de fabrication permet d’obtenir une matrice de plots d’hydrogel de 60 µm de diamètre et d’une hauteur de 6 µm en moyenne. En outre, il a été démontré que les oligonucléotides immobilisés dans les plots pouvaient détecter de façon quantitative et sélective les cibles complémentaires présentes dans l’échantillon analysé en utilisant une détection par colorimétrie ou par chimiluminescence. / The work reported in this thesis focuses on biomolecules immobilization for the development of multiparametric analysis tools on a biochip coupled with a colorimetric detection, applied to the characterization of biological samples and to diagnosis.The first concern was the development of high-throughput automated hybridization tests and immunotests on a filtration plate. This method led to the elaboration of an automated platform for extended blood group genotyping in collaboration with the Etablissement Français du Sang Rhône-Alpes (EFS-RA). It enables to analyze 96 samples in four hours and to characterize six genotypes per sample. Its analytical performances were validated on a panel of 293 blood donors.The second part of this work aimed to elaborate a new strategy for oligonucleotide immobilization on an innovative polymer (PolyshrinkTM) for the development of miniaturized analysis systems. Several approaches were evaluated and led to an in-situ immobilization of oligonucleotides in hydrogel dots technique. This method leads to 6 µm hydrogel dots with a diameter of 60 µm. Moreover it was demonstrated that such immobilized oligonucleotides were able to detect targets specifically and quantitatively using either a chemiluminescent or a colorimetric detection.

Abstract There are eight foods that contribute to food allergies in the western world and peanut is the most common. Currently, there are no medical treatments that can cure an individual of food allergy, so avoidance of the allergic food is the only option. In the United States, there are three immunodominant allergic proteins accountable for patient sensitization to peanut, Arachis hypogea 1, 2, and 3 (Ara h 1, Ara h 2, Ara h 3). Therefore, research into why peanuts are more allergic than other foods that have homologous proteins is critical and may be obtained by studying the structural and allergenic properties of individual allergens and the changes that occur due to food processing. In this study, the basic and acidic subunits of Ara h 3 were cloned, expressed, and purified, and compared with each other and with the native Ara h 3 purified from peanut for differences in binding to IgE from peanut allergic individuals. Also, an in vitro Maillard reaction was performed on purified native raw Ara h 3 and patient serum IgE western blots were performed. This study concluded that an in vitro Maillard reaction enhanced IgE binding to Ara h 3, IgE binding to native Ara h 3 was in most cases higher than to the recombinant Ara h 3 subunits, and recognition of the acidic subunit was much higher than the and basic subunits in both the recombinant and native forms of the protein were investigated. Keywords:

Allergy, as one of the worldwide most frequent pathologies, belongs to illnesses with constantly growing incidence among young children. In genetically predisposed individuals, dendritic cells are able to polarize the immune response of Th2 in contact with the allergen. Postnatal probiotic supplementation could be one the preventive measure to prevent the development of allergic diseases. It has been shown that introduction of selected probiotic strains or mixtures can prevent development of allergy. In this diploma thesis, the capacity of probiotic strain Escherichia coli O83:K24:H31 (E. coli O83) to support maturation of dendritic cells (DC) and polarization of immune responses was tested. Introduction of this probiotic vaccine called Colinfant Newborn appears to be suitable preventive measure, lowering allergy incidence in children with predisposition to development of allergy. The aim of this diploma thesis was to observe capacity of E. coli O83 to support maturation of the two main subpopulations of dendritic cells (myeloid dendritic cells - mDC and plasmacytoid dendritic cells - pDC) in cord blood of newborns of healthy mothers (children with relatively low risk for allergy development) and allergic mothers (children with relatively high risk for allergy development). To achieve this goal,...

Allergy as one of the most frequent pathologies worldwide belongs to illnesses with constantly increasing incidence even amongst young children. It develops in genetically predisposed individuals whose dendritic cells (DC) are, after contact with allergen, able to polarize the immune response predominantly to Th2, while Th1 response is supressed. One of the possible preventive measures to avoid an allergic disease developement could be an early postnatal supplementation of chosen probiotic bacterial strains or their mixtures. One of them is a well characterized strain Escherichia coli O83:K24:H31 (E. coli O83). Administering of this probiotic vaccine called Colifant Newborn is showing to be an effective prophylaxis to decrese the incidence of allergies in children with predisposition to their developement. The aim of my diploma thesis was to experimentally confirm the capacity of E. coli O83 to support maturation of two main subpopulations of newborn DC available from cord blood: myeloid dentritic cells - mDC and plasmacytoid dentritic cells - pDC. This DC subpopulations were isolated from cord blood of children born to healthy (non-allergic) mothers who had a low risk of allergy development or from children of allergic mothers who had an increased risk of allergy development. Subsequently, after...

Contexte : L’organisme en développement est très sensible à son environnement. Plusieurs études épidémiologiques ont suggéré la toxicité développementale d’une dizaine de polluants suite à des expositions prénatales. L’objectif général de cette thèse est d’évaluer les conséquences des expositions à des polluants chimiques (consommation de produits de la mer comme vecteur de contamination, solvants organiques et insecticides organophosphorés) pendant la grossesse sur le développement de l’enfant à 2 ans en se focalisant sur le développement neuro-comportemental, le développement respiratoire et immunitaire et le développement staturo-pondéral. Matériel et méthodes : Ce travail s’est appuyé sur la cohorte mère-enfant PELAGIE, mise en place en Bretagne entre 2002 et 2006. Près de 3500 femmes ont été incluses en début de grossesse et environ 1500 couples mère-enfant ont été suivis à 2 ans. Les expositions ont été évaluées en début de grossesse à partir de questionnaires, de matrices emplois-expositions ou de dosage de biomarqueurs d’exposition. Les indicateurs de santé ont été mesurés lors du suivi à 2 ans par questionnaire permettant de recueillir des éléments sur le comportement, les manifestations respiratoires à type de sifflement, les maladies allergiques et la croissance entre la naissance et 2 ans. Résultats : L’exposition professionnelle prénatale aux solvants organiques était associée à des déficits de l’attention/hyperactivité et des niveaux d’agressivité plus importants chez l’enfant à 2 ans. Cette exposition n’était pas associée avec les manifestations respiratoires et allergiques. Nous avons aussi montré que la consommation maternelle de coquillages et crustacés pendant la grossesse était associée à une augmentation du risque d’allergie alimentaire chez l’enfant. Enfin, l’exposition prénatale aux insecticides organophosphorés a été associée à une diminution de la vitesse de croissance en taille à 2 ans. Conclusion : Ce travail renforce l’hypothèse de l’implication de l’exposition prénatale aux polluants chimiques de l’environnement, y compris à faible dose, dans l’origine développementale de la santé et des maladies. / Background: The organism is very sensitive to environment during its developmental period. Number of epidemiological studies has suggested the developmental toxicity of about ten chemical pollutants after prenatal exposure. The general objective of the thesis is to explore the effect of prenatal exposure to certain chemical pollutants (organic solvents, organophosphates pesticides and maternal consumption of fish and shellfish (vectors of pollutants)) on child development at age 2. Methods: This thesis is based on the PELAGIE mother-child cohort that was set up in 2002, in Brittany (FRANCE). In total, 3421 women were included in this cohort at the beginning of pregnancy and 1500 mother- child pairs were followed when the child was 2 years old. Exposures were evaluated at the beginning of pregnancy from questionnaires, job-exposure matrices or measurement of biomarkers of exposure. Health indicators were measured at the 2 years follow-up. At follow-up, questionnaires allowed to obtain information on child behaviour, respiratory manifestations like wheezing, allergies (eczema and food allergy) and growth between birth and the age of two. Results: Prenatal occupational exposure to solvents was associated with higher level of hyperactivity and attention deficit at age 2. This exposure was not associated neither with respiratory nor with allergic manifestations. We also observed that maternal shellfish consumption during pregnancy was associated with a higher risk of food allergy in preschoolers. Finally, higher prenatal exposure to organophosphate pesticides was associated with a decrease height growth velocity at age 2. Conclusion: The present thesis based on the PELAGIE study supported for the hypothesis that prenatal exposure to environmental chemicals may be implicated in the developmental origin of health and diseases.

Some previously described environmental associations for atopic eczema may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple atopic eczema risk factors. The International Study of Asthma and Allergies in Childhood (i.e, ISAAC) Phase Three surveyed children in schools (the sampling unit) regarding atopic eczema symptoms and potential risk factors. We assessed the effect of these risk factors on atopic eczema symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. Overall, 546,348 children from 53 countries were included. At ages 6–7 years, the strongest individual-level associations were with current paracetamol use (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.37–1.54), which persisted at school-level (OR = 1.55, 95% CI = 1.10–2.21), early-life antibiotics (OR = 1.41, 95% CI = 1.34–1.48), and early-life paracetamol use (OR = 1.28, 95% CI = 1.21–1.36), with the former persisting at the school level, whereas the latter was no longer observed (OR = 1.35, 95% CI = 1.00–1.82 and OR = 0.94, 95% CI = 0.69–1.28, respectively). At ages 13–14 years, the strongest associations at the individual level were with current paracetamol use (OR = 1.57, 95% CI = 1.51–1.63) and open-fire cooking (OR = 1.46, 95% CI = 1.33–1.62); both were stronger at the school level (OR = 2.57, 95% CI = 1.84–3.59 and OR = 2.38, 95% CI = 1.52–3.73, respectively). Association with exposure to heavy traffic (OR = 1.31, 95% CI = 1.27–1.36) also persisted at the school level (OR = 1.40, 95% CI = 1.07–1.82). Most individual- and school-level effects were consistent, tending to exclude reverse causation. / Revisión por pares

INTRODUÇÃO: A importância da resposta mecânica do parênquima pulmonar na fisiopatologia da asma tem sido recentemente reconhecida. O óxido nítrico é um mediador que controla o tônus muscular liso das vias aéreas, porém este efeito no parênquima pulmonar periférico ainda não foi previamente investigado. Nossa hipótese é que a inibição crônica das óxido nítrico sintases por meio do tratamento com L-NAME (falso substrato para todas as óxido nítrico sintases) pode modular a mecânica do parênquima pulmonar, o recrutamento eosinofílico e o remodelamento da matriz extracelular em modelo de inflamação alérgica crônica pulmonar em cobaias. MÉTODOS: Os animais foram expostos a sete inalações com soro fisiológico ou com ovoalbumina em doses crescentes (1~5mg/ml - 4 semanas) e tratadas ou não com L-NAME (60 mg/kg/ por dia /por animal) na água de beber. Setenta e duas horas após a sétima inalação os animais foram anestesiados, exsanguinados e a mecânica oscilatória do parênquima pulmonar foi medida na condição pré e após desafio (0.1%). Utilizando a técnica de morfometria foram avaliadas a densidade de eosinófilos, o número de células nNOS e iNOS positivas, a densidade de actina, das fibras colágenas e das fibras elásticas bem como a proporção de volume de 8-iso-PGF2 no septo alveolar. RESULTADOS: Os animais que foram expostos à ovoalbumina apresentaram um aumento da resistência e da elastância tecidual (resposta basal e após desafio antigênico), na densidade de eosinófilos, no número de células nNOS e iNOS positivas, na densidade de fibras colágenas e de fibras elásticas bem como na expressão de 8-isoPGF2 no septo alveolar comparativamente aos grupos controles (p<0,05). O tratamento com L-NAME em animais expostos à ovoalbumina atenuou todas as respostas de mecânica do tecido pulmonar periférico (p<0, 01), reduziu o número de células nNOS e iNOS positivas (p<0.01), o conteúdo de fibras elásticas (p<0,001) e de 8-iso-PGF2 no septo alveolar (p<0,001). No entanto, este tratamento não afetou o número total de eosinófilos e o conteúdo de fibras colágenas. Este trabalho sugere que o óxido nítrico contribui para a constrição do parênquima pulmonar e para a deposição de fibras elásticas neste modelo. Estes efeitos foram associados à ativação de iNOS e nNOS em células do parênquima distal e aumento na via do estresse oxidativo / The importance of lung tissue mechanical responses in asthma pathophysiology has been recently recognized. Although nitric oxide (NO) is a mediator that controls smooth muscle tonus control in the airways, its effects on lung tissue responsiveness has not been previously investigated. We hypothesized that chronic nitric oxide synthase inhibition by L-NAME (false substrate for all nitric oxide synthases) treatment may modulate lung tissue mechanics, eosinophilic recruitment and extracellular matrix remodeling in a model of chronic pulmonary allergic inflammation. Guinea pigs were submitted to seven normal saline or ovalbumin exposures with increasing doses (1~5mg/mL-4weeks) and treated or not with L-NAME in drinking water. Seventy-two hours after the seventh inhalation the animals were anesthetized, exsanguinated, and oscillatory mechanics of lung tissue strips was performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, the number of iNOS and nNOS-positive cells, the density of actin, the collagen and elastic fibers content and the volume proportion of 8-iso-PGF2 in the alveolar septa. Ovalbumin-exposed animals presented an increase in baseline and maximal tissue resistance and elastance responses, eosinophil density, in the number of iNOS and nNOS positive cells, in the amount of collagen and elastic fibers and in the volume proportion of 8-iso-PGF2 in the alveolar septa compared to controls (p<0.05). L-NAME treatment in ovalbumin-exposed animals attenuated all lung tissue mechanical responses (p<0.01), reduced the number of iNOS and nNOS positive cells (p<0.01), elastic fiber content (p<0.001) and 8-isoPGF2 in the alveolar septa (p<0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fibers deposition in this model. These effects were associated to iNOS and nNOS activation in pulmonary parenchyma and with an increase in oxidative stress pathway activation

A prevalência de sintomas de asma, broncoespasmo induzido pelo exercício (BIE), hiperresponsividade brônquica (HRB) e alergia em atletas que praticam modalidades de alto rendimento e longa duração tem aumentado nas últimas décadas e tem sido estudada principalmente em atletas de inverno e nadadores. No entanto, a prevalência de sintomas de asma e alergia e os mecanismos inflamatórios envolvidos no BIE que ocorre em corredores de longa distância permanecem pouco conhecidos. Objetivos: O presente estudo tem como objetivo avaliar a prevalência de sintomas de asma e alergia em corredores de longa distância de elite e investigar os mecanismos inflamatórios envolvidos no BIE nos atletas sem histórico de asma. Casuística e Métodos: Este estudo foi realizado em duas fases: na Fase I, foi avaliada a prevalência de sintomas de asma e alergia em 201 corredores de longa distância, através da aplicação dos questionários ISAAC e AQUA©. Na Fase II, foram avaliados os mecanismos inflamatórios envolvidos no BIE de 40 corredores que não apresentaram sintomas de asma na Fase I e que foram selecionados aleatoriamente. Nesta fase, os atletas compareceram ao laboratório em três momentos, com intervalo máximo de duas semanas entre cada visita, e foram submetidos às seguintes avaliações 1º) escarro induzido e teste cardiopulmonar máximo, 2º) broncoprovocação por metacolina e, 3º) óxido nítrico no ar exalado (FeNO), metabólitos LTE4 e 9alfa, 11beta-PGF2 e teste de hiperventilação eucápnica voluntária (HEV). Resultados: A prevalência de sintomas de asma e alergia foi de 6,5% e 60,5%, respectivamente. Ao analisar as questões do AQUA©, observou-se alta frequência de sintomas de BIE (62,3%) e rinite (56,6%). Os sintomas de alergia não foram associados a variáveis como gênero, idade, experiência em corridas de longa distância, volume de treinamento semanal e desempenho em provas de meia maratona e maratona. Verificou-se ainda que a prevalência de BIE foi de 27,5%. Quando comparados os atletas BIE+ e BIE- não foram observadas diferenças nos valores de VEF1 absoluto, nas medidas antropométricas, nas características de treinamento e também no desempenho. Os atletas BIE+ relataram mais sintomas de alergia (p=0,03), se mostraram mais responsivos à metacolina (p=0,01), apresentaram maior porcentagem de eosinófilos no escarro (p=0,03) e níveis mais elevados de FeNO (p < 0,001*) quando comparados aos atletas BIE-. Os níveis urinários de LTE4 e 9alfa, 11beta-PGF2 basais e após 60 minutos do teste de HEV foram similares entre os grupos BIE+ e BIE-, no entanto, ao comparar os níveis destes mediadores antes e após o teste de HEV, observou-se uma diminuição nos níveis de LTE4, apenas nos atletas BIE- (p=0,04). Conclusões: Corredores de longa distância apresentam elevada prevalência de sintomas de alergia e BIE e baixa prevalência de sintomas de asma. Além disto, os atletas BIE+ referem mais sintomas de alergia, são mais hiperresponsivos à metacolina, apresentam um padrão inflamatório eosinofílico e elevados níveis de FeNO embora sem diferenças nos níveis basais dos metabólitos do mastócito / An increased prevalence of asthma and allergic symptoms, exercise-induced bronchoconstriction (EIB) and bronchial hyperresponsiveness (BHR) has been observed in elite and endurance athletes, especially winter sports athletes and swimmers. However, the occurrence of allergy symptoms and the inflammatory mechanisms involved in the EIB that occurs in long distance runners remains poorly known. Objectives: the aims of the present study were to assess the prevalence of symptoms of asthma and allergy in long distance runners and to investigate possible inflammatory mediators involved in the EIB that occurs in those without asthma history. Methods: This cross sectional study was performed in two phases. In Phase I, the prevalence of symptoms of asthma and allergy was assessed in 201 long distance runners using ISAAC and AQUA© questionnaires. In Phase II, 40 athletes were randomly selected among those who did not present asthma history and they performed the following measurements: induced sputum, cardiopulmonary exercise testing, methacholine bronchoprovocation challenge, exhaled nitric oxide (FeNO), urinary collection to quantify LTE4 and 9alfa, 11beta-PGF2 metabolites and eucapnic voluntary hyperventilation test (EVH). Results: The prevalence of asthma and allergy symptoms was 6.5% and 60.5%, respectively. In addition, we observed a high frequency of EIB symptoms (62.3%) and rhinitis (56.6%). Allergy symptoms were not associated with anthropometric characteristics, running experience, weekly training volume and best half-marathon and marathon performance. The prevalence of EIB was 27.5% and no difference in baseline lung function, anthropometric data as well as training and performance characteristics was observed between athletes with (EIB+) and without (EIB-) EIB. EIB+ athletes reported more allergy symptoms (p=0.03) and were more resposive to methacholine (p=0.01) than EIB- athletes. A higher percentage of eosinophils in the induced sputum (p=0.03) and levels of FeNO (p < 0.001*) were observed in EIB+ athletes. However, there was no difference in the urinary levels of LTE4 and 9alfa, 11beta-PGF2 either at baseline or after EVH test. Conclusions: Long distance runners have a high prevalence of allergy symptoms and EIB and a low prevalence of asthma symptoms. Moreover, EIB+ athletes report more symptoms of allergy and present airway hyperresponsiveness, eosinophilic inflammation and increased levels of exhaled nitric oxide, without difference in the baseline levels of mast cell metabolites

Klinische, epidemiologische und experimentelle Daten deuten darauf hin, dass Autoimmunkrankheiten wie z.B. rheumatoide Arthritis, multiple Sklerose oder Typ I Diabetes durch Infektionen ausgelöst oder verschlimmert werden können. Bis heute ist jedoch nicht bekannt, welche molekularen und zellulären Mechanismen den Zusammenhang zwischen Infektion und Autoimmunität vermitteln. Eine Hypothese, die diesen Zusammenhang zu erklären versucht, ist die Hypothese der molekularen Mimikry. Dieser Hypothese zufolge sind kreuzreaktive Lymphozyten, die sowohl Selbst- als auch Fremdantigene erkennen, für die Induktion von Autoimmunität verantwortlich. Die Hypothese der molekularen Mimikry erklärt die Kreuzreaktivität von Lymphozyten durch Sequenzhomologie oder Identität von Selbst- und Fremdantigenen. Wir haben diese Hypothese an zwei Modellen, der chronischen Lyme Arthritis und einem Maus Modell der multiplen Sklerose, getestet und dabei festgestellt, dass Kreuzreaktivität von Lymphozyten weitaus häufiger ist als bis vor kurzem noch vermutet wurde. Wir konnten weiterhin zeigen, dass nicht die Primärstruktur sondern definierbare strukturelle Motive die Ursache für die Kreuzerkennung von Selbst- und Fremdpeptiden sind, und das Kreuzreaktivität in den seltensten Fällen von pathogenetischer Relevanz ist. Die Vorstellung, immunologische Kreuzreaktivität zwischen einem definierten mikrobiellen Antigen und einem definierten Selbstantigen sei für die Pathogenese von Autoimmunkrankheiten verantwortlich, ist also zu einfach. Der zweite Schwerpunkt dieser Arbeit ist die immunologische Analyse eines von uns charakterisierten Th2-spezifisch exprimierten Moleküls, T1/ST2. Wir konnten zeigen, dass T1/ST2 auf Th2, nicht jedoch Th1-Zellen exprimiert wird; dass die Expression von T1/ST2 ex vivo die Lokalisation aktueller Th2-Antworten widerspiegelt; und dass T1/ST2 von funktioneller Bedeutung für die Th2 Zellen ist: Kreuzvernetzung des T1/ST2 Moleküls durch einen T1/ST2-spezifischen monoklonalen Antikörper induziert Proliferation und die Produktion von Typ 2 Zytokinen. In vivo läßt sich durch Applikation des löslichen Antikörpers gegen T1/ST2 die pathogene Th2-Immunantwort im Mausmodell von Asthma modulieren. T1/ST2 ist also ein Kandidat für die gezielte immunmodulatorische Therapie Th2-dominierter Erkrankungen wie Asthma und Allergie. / Clinical, epidemiological, and experimental data suggest that infections can sometimes trigger or exacerbate autoimmune diseases such as multiple sclerosis, type I diabetes, or rheumatoid arthritis. To date, the molecular and cellular mechanisms leading from infection to autoimmunity have not been defined. The molecular mimicry hypothesis proposes that crossreactive lymphocytes that recognize both self- and microbial antigens are key factors in the pathogenesis of autoimmunity. According to the molecular mimicry hypothesis, sequence identity or marked sequence similarity between self- and microbial antigens is the cause of such crossreactivity. We have examined the molecular mimicry hypothesis systematically in two different models: treatment-resistant Lyme arthritis and experimental autoimmune encephalitis (EAE). The major findings were: i) crossreactivity at the level of peptide recognition by T cells is far more frequent than previously expected; ii) structural criteria rather than sequence similarity determine cross-recognition; iii) immunoregulatory mechanisms normally prevent pathogenic effects mediated by crossreactive lymphocytes. Thus, the idea that crossrecognition of a defined microbial peptide and a particular self-peptide would explain autoimmunity is most likely too simple. The other major topic of this work was the immunological analysis of T1/ST2, a Th2-specific molecule that we characterized. Here, we could show that T1/ST2 is expressed on Th2 but not Th1 cells. Furthermore, T1/ST2 expression can be used to identify sites of ongoing Th2 reactions directly ex vivo. Most importantly, T1/ST2 is important for Th2 effector functions: crosslinking of T1/ST2 via a T1/ST2-specific monoclonal antibody induces proliferation and type 2-cytokine production. In vivo, administration of the soluble antibody against T1/ST2 ameliorates the immunological parameters of bronchial hyperreactivity in a murine model of asthma. Thus, T1/ST2 is a candidate target for therapeutic immunomodulation of diseases such as allergy and asthma.

Vergleichsweise wenige Texte in den Printmedien beschäftigen sich mit Allergie als Gegenstand öffentlichen Interesses. Deshalb untersucht die Dissertation die Darstellung von Allergien in Lifestyle-Magazinen im englisch- und amerikanischsprachigen Raum. Die vorliegende Arbeit befasst sich mit der Verbreitung von medizinischem Wissen durch die Medien. Sie zeigt, ob und wie die Medien zu Aufklärung und Information über Krankheiten, deren Relevanz, Diagnostik und Therapie, beitragen. Sie geht dabei besonders auf den Bedeutungsbereich von Wörtern ein, die als Metaphern benutzt werden. Das Fundament der Überlegungen bildet der Essay „Illness as Metaphor“ von Susan Sontag, in dem sie die Darstellung von Krankheiten und die Benutzung von Stereotypen abhandelt und Fragen, die im Zusammenhang mit Krankheit als sozialer und kultureller Angelegenheit stehen, aufwirft. Um den populärwissenschaftlichen Diskurs der analysierten Artikel in dieser Arbeit zu verstehen, wurde die von Jürgen Link entwickelte Diskursanalyse herangezogen, die sich eng an die Diskurstheorie Foucaults anlehnt. Die semiotischen Deutungsansätze werden mit Hilfe der Untersuchungen von Roland Barthes erklärt. Ziel der Arbeit ist es zu zeigen, wie die verschiedenen Diskurse ineinander greifen, welcher Mechanismus sich dahinter verbirgt und wo Ansatzpunkte für eine sachgerechte publizistische Behandlung des Themas liegen. Der Nutzen von Metaphern in der Beschreibung von Krankheiten liegt darin, dass sie kollektive Gefühlslagen ansprechen und den Denkraum des Möglichen erweitern. Dieser Aspekt ist besonders wichtig, da das Wort Allergie zu einer praktischen und populären Metapher für eine Reihe persönlicher, beruflicher oder politischer Antipathien geworden ist. Obwohl allergische Erkrankungen in der modernen Welt immer häufiger auftreten, räumen ihnen die Medien noch nicht den Platz ein, den sie -- auch ausgehend von der volkswirtschaftlichen Bedeutung der Erkrankungen -- dringend haben müssten. / Only a few print media focus on allergies as a matter of public interest. For this reason the dissertation analyzes the presentation of allergies in English and American lifestyle magazines. This thesis examines the propagation of medical knowledge via the media. It shows if and how the media contribute to health education and information about illness, its relevance, diagnostic investigation as well as therapy. The main focus is on those words which are used as metaphors. They represent an important subject of Susan Sontag''s essay „Illness as Metaphor“ which demonstrates the presentation of illness, the use of stereotypes and thus raises issues about illness being a social and cultural matter of interest. To understand the popular scientific discourse of this dissertation Jürgen Links'' discourse analysis is being used which follows closely Foucault''s theory. The semiotic interpretation is supported by the theories developped by Roland Barthes. This dissertation aims to show how the different discourses intertwine, to bring to fore the underlying mechanisms as well as an appropiate journalistic approach. The benefit of using metaphors when describing illness is that the collective state of mind is addressed and thus the range of thinking will be broadened. This aspect is especially important because the word allergy became a convenient and popular metaphor for a number of personal, professional or political aversions. Although allergies are dramatically on the raise in the modern world, their significance is not recognized yet by the media in their complexity as it should be the case, especially against the backdrop of the economic relevance of that illness