Mon travail, lors de ma thèse, avait pour but d’étudier la différentiation des lymphocytes Tfh, ainsi que leur fonction et leur régulation dans la pathogenèse de la DA. Pour cela, j’ai utilisé un modèle murin précédemment établi au sein de notre laboratoire consistant en l’application topique de MC903 (un analogue de la vitamine D3) induisant la production de TSLP par les kératinocytes et, par conséquence, la réponse immunitaire Th2 et la pathogenèse de la DA. mon travail doctoral s’est porté sur la différentiation des lymphocytes Tfh, leur production cytokinique ainsi que la formation des centres germinatifs dans le contexte d’un modèle murin de DA induite par le MC903. Mes études ont démontré un rôle critique joué par TSLP dans la réponse Tfh et ont exploré le rôle potentiellement joué par les cellules dendritiques langerine+ et la signalisation OX40L dans le développement des réponses Tfh et de type 2. Ceci nous a permis d’approfondir nos connaissances concernant les mécanismes sous-tendant la réponse immunitaire de type 2 dans la pathogenèse de la DA. Dans la deuxième partie de ma thèse, nous avons examiné le rôle de MC903 dans la régulation de l’inflammation due au psoriasis, en utilisant un modèle de psoriasis induit par l’Aldara. Nous avons montré que MC903 inhibe l’axe 23/IL-17/IL-22 chez les souris souffrant de psoriasis. De plus, cette inhibition semblait être dose-dépendante. Nous avons en outre exploré le rôle de TSLP et VDR dans la médiation de cet effet dû au MC903. / My thesis aimed at studying the Tfh cell differentiation, function and regulation in AD pathogenesis. To this aim, I employed our previously established AD mouse model in which MC903 (a vitamin D analog) topical treatment on the skin induces TSLP production bykeratinocytes, promotes Th2 cell response and drives the pathogenesis of AD. my thesis work investigated Tfh cell differentiation, its cytokine expression and germinal center formation using MC903-induced AD mouse model. By exploring the role of TSLP,Langerin+ DCs and OX40L signaling in Tfh cell differentiation and regulation, my study provides novel insights into the mechanisms underlying the type 2 immune response in AD pathogenesis. In the second part of my study, we examined the role of MC903 in regulating the psoriatic inflammation using Aldara-induced psoriasis model. We showed that MC903 inhibited IL-23/IL-17/IL-22 axis in mouse psoriasis. Moreover, this inhibition exhibited a dose-dependent manner. We further explored the role of TSLP and VDR in mediating such effect of MC903.

A dermatite atópica é uma doença de pele de caráter inflamatório crônico que normalmente precisa de tratamento com glicocorticóide tópico. O objetivo deste estudo foi avaliar o impacto da Dermatite atópica no consumo de nutrientes, no estado nutricional e no metabolismo ósseo de crianças com dermatite atópica moderada e grave comparadas à crianças saudáveis. Foram incluídas neste estudo 60 crianças de 4 a 12 anos com AD moderada/grave e 54 controles. O consumo alimentar foi avaliado por três recordatórios de 24 horas. O estado nutricional foi determinado pelo z-escore de altura para idade, peso por idade e do índice de massa corporal. Os marcadores ósseos séricos foram 25OH vitamina D, fosfatase alcalina óssea, cálcio sérico, fósforo, PTH, osteocalcina, CTX e cortisol. Os pacientes e familiares foram questionados quanto à fraturas, exposição solar e escore de atividade física. Por meio de densitometria dupla de Raio-X avaliou-se o conteúdo mineral ósseo (CMO), a densidade mineral óssea (DMO) e o z-score da coluna lombar, do fêmur total e do corpo inteiro. As crianças com dermatite atópica usavam glicocorticóide tópico em média por 3,9 ±1,81 anos. O tempo de exposição solar foi menor nas crianças com dermatite atópica. O consumo alimentar evidenciou um alto consumo de proteínas em ambos os grupos, e a ingestão de gordura foi mais baixo na crianças com DA. A média consumida de cálcio e vitamina D foi abaixo da recomendação nutricional em ambos os grupos. As crianças com DA apresentaram mais casos de rinite, asma e alergia alimentar do que o grupo controle. Segundo o zscore de altura para idade as crianças com DA foi significativamente mais baixas quando comparadas com o grupo controle. O CTX sérico foi menor no grupo DA. O CMO da coluna lombar foi mais baixo nas crianças com DA, e o CMO, a DMO e o z-score do fêmur total também foram significativamente menores no grupo DA do que no grupo controle. Neste grupo de crianças com DA, estudado o uso do glicocorticóide tópico pode ter diminuído a altura para idade, e a massa óssea. / Atopic dermatitis is an inflammatory allergic skin disease that often requires glicocorticosteroids therapy. The aim of this study was to determine the atopic dermatitis impact on food ingestion, nutritional status and bone mass in children with moderate to severe AD compared with a control group. Food ingestion was evaluated with 3 days 24-hour food recordathory. Nutritional status was determined with height to age z-score, weight for age z-score and BMI z-score. Bone markers measured in serum were 25OH vitamin D, bone phosphatase alkaline, CTX, serum calcium, phosphorus, osteocalcin, PTH and cortisol. Information on lifestyle parameters, bone fractures, sun exposure and physical activity were collected by use of a standardized questionnaire. Lumbar spine, total femur and whole body, bone mineral content (BMC), bone mineral density (BMD) and z-score was measured by dual-energy X-ray absorptiometry in 60 children (age 4-12years) with moderate to severe AD and 54 health controls, with the same age. In children, low BMD was defined as a Z-score less than -2. The AD children used topic glicocorticosteroids for a mean of 3,9 ±1,81 years. The sun exposure was lower in the AD group. Food ingestion showed high protein ingestion levels in both groups, and the fat consumption was lower in the AD children. The calcium and vitamin ingestion were bellow the recommendations in the two groups. Children with AD had more riniths, asthma and food allergy then control group. The CTX was lower in the AD group. The children with AD were significantly smaller according to the height for age zscore. There was significant smaller BMC on lumbar spine, and in the BMC, BMD and z-score in the total femur on the AD children. Low BMD occured more frequently in this population of children with moderate to severe AD compared with the control group. Use of topical glicocorticosteroids in the previous could be 5 years associated with the decrease in BMD.

Introdução: Eczemas são manifestações inflamatórias da pele. Na infância se destacam a dermatite atópica (DA) e a dermatite de contato (DC). Os testes de contato correspondem a um método auxiliar para diferenciar a dermatite de contato por irritante primário (DCIP) da dermatite de contato alérgica (DCA) e definir a etiologia da DCA. Nos pacientes com DA, têm a faculdade de também auxiliar na identificação de substâncias que possam estar contribuindo para a piora do quadro. Objetivos: verificar a frequência de testes de contato positivos em crianças com hipóteses diagnósticas de DC e de DA associada ou não à DC; obter os principais sensibilizantes nessa faixa etária e comparar os dados obtidos entre os grupos de pacientes com DC e DA. Métodos: Durante o período entre julho de 2007 e agosto de 2009, 62 crianças com idades entre 2 e 12 anos foram submetidas aos testes de contato com a bateria padrão e/ou bateria de cosméticos de testes de contato padronizadas pelo Grupo Brasileiro de Estudos em Dermatite de Contato. As leituras foram realizadas em 48 e 96 horas. Resultados: Entre os 62 pacientes submetidos aos testes de contato, 38 pacientes apresentaram pelo menos um teste de contato positivo e 24, todos negativos. Entre os 44 pacientes com hipótese diagnóstica inicial de DA, 19 tinham DA associada à DCA. Entre os 18 pacientes com hipótese diagnóstica inicial de DC, 12 apresentavam DCA. No total, foram encontrados 76 testes positivos, sendo 53 (70%) relevantes, e 23 (30%) não relevantes com a história clínica do paciente. Os pacientes com DA apresentaram mais testes positivos não relevantes do que os pacientes com hipótese diagnóstica apenas de DC, e essa diferença foi estatisticamente significativa.( 2 = 6,55 e p = 0,01 ). Considerando os testes relevantes com a história clínica, o sulfato de níquel foi o principal sensibilizante com 14 (22,6%) testes positivos, a neomicina foi o segundo sensibilizante mais comum com sete testes positivos (11,3%), e a terceira substância mais comum foi o cloreto de cobalto com quatro (6,4%) testes positivos. Testes não relevantes foram encontrados em 30% do total de substâncias com testes positivos. O timerosol foi positivo em 11 casos, porém em oito pacientes com DA não foram relevantes com a história clínica. Conclusões: Pacientes na faixa etária entre 2 e 12 anos com DA e DC apresentaram testes de contato positivos, e não houve diferenças quanto à frequência dos testes positivos entre esses dois grupos. Os principais sensibilizantes relevantes com a história clínica foram o sulfato de níquel, a neomicina e o cloreto de cobalto, o que está de acordo com vários estudos na literatura. Pacientes com DA apresentaram mais testes falso-positivos que os pacientes com DC, possivelmente por um defeito da barreira cutânea dos pacientes com DA, e maior exposição precoce aos medicamentos tópicos ou emolientes para o controle da DA. Teste de contato em crianças pode ser considerado importante ferramenta para auxiliar no diagnóstico dos eczemas, identificando o agente causador da DC ou de piora nos casos de DA, e deve ser levado em conta em todos esses pacientes / Eczema is a cutaneous inflammatory manifestation in some dermatosis. In children, we highlight atopic dermatitis (AD) and contact dermatitis (CD). Patch tests help to differentiate irritative contact dermatitis (ICD) from allergic contact dermatitis (ACD), and define the etiology of allergic contact dermatitis. In patients with AD, it may also help to identify substances that may contribute to the worsening of this dermatosis. Objectives: To determine the frequency of positive patch tests in children with diagnosis of CD and AD with or without CD; to detect the main sensitizers in this group and compare the results between the groups of patients with CD and AD. Methods: From July 2007 to August 2009, 62 children aged between 2 to 12 years old were patch tested with the Brazilian standard battery of patch tests and cosmetic series. The readings were taken at 48 and 96 hours. Results: Thirty-eight patients had at least one positive patch test reactions and 24, all negative. Among the 44 patients with initial diagnosis of AD, 19 were associated with ACD. Among the 18 patients with initial diagnosis of CD, 12 had ACD. In total, there were 76 positive tests, 53 (70%) relevant, and 23 (30%) not relevant to the patient\'s clinical history. Patients with AD showed more positive tests not relevant than patients with diagnosis of CD only, and this difference was statistically significant. (2 = 6.55 and p = 0.01). Considering the relevant tests, nickel sulphate was the main allergen with 14 (22.6%) positive tests, neomycin was the second with seven positive tests (11.3%), and the third substance was cobalt chloride with four (6.4%) positive tests. Tests not relevant were found in 30% of the total of the positive tests. Thimerosol was positive in 11 cases, but in eight patients with AD were not relevant to the clinical history. Conclusions Patients aged between 2 to 12 years old with AD and CD had positive tests, and there were no differences in the frequency of positive tests between these two groups. The main sensitizers, relevant to the clinical history were nickel sulfate, neomycin and cobalt chloride. This result is consistent with several studies in the literature. Patients with AD showed more false-positive tests than patients with CD, possibly due to a defective skin barrier of AD patients, and earlier exposure to topical emollients and treatments for the control of AD. Patch test in children can be considered an important tool for the diagnosis of eczema, identifying the causative agent of CD or worsening cases of AD, and should be performed in all these patients. The correct interpretation of the patch tests is essential to evaluate the association of ACD in patients with AD and to identify the causative agent of the ACD

O objetivo deste trabalho e o desenvolvimento de roupas utilizando malha de linho para uso como primeira camada em contato direto com o corpo em usuários com dermatite atópica. Roupas disponíveis para essas pessoas com pele sensível, incluindo algumas com algodão, muitas vezes provocam irritação na pele e uma malha de linho pode ser uma boa opção de uso, com base em suas reconhecidas propriedades de contato saudável ao corpo humano, principalmente em climas quentes. Protótipos de malhas consideradas pelo autor como clássicas ou oclusivas e outras como não oclusivas foram produzidas com algodão, fibras descontinuas de poliéster e linho em estrutura jérsei de malharia circular. As malhas foram confeccionadas em roupas para um teste de uso experimental em 4 crianças entre 5-8 anos de idade, sendo 2 delas saudáveis e duas com dermatite atópica, previamente avaliadas por um dermatologista. O resultado final demonstrou um bom grau de tolerância por todos os usuários quanto ao uso da malha com linho em contato direto com a pele. As malhas não oclusivas foram as que apresentaram os melhores índice de permeabilidade ao ar,atributo que pode evitar o bloqueio da transpiração insensível durante rotinas diárias, minimizando o abafamento, desconforto térmico e potencial gatilho de irritação da pele. Câmera infravermelha foi utilizada como uma ferramenta adicional na Avaliação térmica durante o uso. Os resultados sugerem que a malha com linho não oclusiva e uma opção viavel de uso pelos portadores de dermatite atópica em clima subtropical como o da cidade de São Paulo. O controle da estabilidade dimensional da malha com linho e amaciantes naturais amigáveis a pele para a lavagem domestica das roupas são desafios que devem ser equacionados em futuros desenvolvimentos / Linen (Linum usitatissimum L.) in single jersey of circular knitting machine for wearer with atopic dermatitis in subtropical climate The purpose of this work is the development of first layer linen knitted structure aiming wearers with Atopic Dermatitis (AD). Available clothing for these sensitive skin people, including some cotton garments, very often presents skin irritation and linen is an option based upon it recognized friendly contact to human body and comfortable wear during hot climates. Classic or occlusive and non-occlusive garments prototypes knitted in single jersey of circular knitting machines with cotton, polyester staple and linen fibers were designed to accomplish an experimental wear test with 4 children with 5-8 years old, 2 with AD and 2 health kids. Voluntaries showed good wear tolerance to knitted linen that presented highest air permeability index that can help to avoid blocking of insensible perspiration during daily routine, minimizing buffering effect and potential trigger of skin irritation. Infrared camera was used as an additional tool for thermal evaluation during use. Results suggest that non-occlusive knitted linen is a possible option for AD wears at subtropical climate like the city of Sao Paulo. Dimensional stability control of nonhocclusive knitted linen and natural home laundry softeners are challenges to be overcome in future developments

Abstract The purpose of the study was to get knowledge of everyday life of children (aged 0–10 years) with atopic dermatitis and their families. An ethnographic approach was used. Different data sets were collected by interviewing, observing and presenting questionnaires. The interviews (n = 24) and observations (n = 24) of the families (n = 7) took place at their homes. Children aged 5–10 years (n = 80), assisted by their parents, filled in a quality of life questionnaire. In the case of children younger than 5 years (n = 174) and families (n = 254), the quality of life questionnaire was filled in by the parents. The severity of atopic dermatitis of each participating child (n = 254) was evaluated by a physician. The professional perspective was introduced into the study in the form of discussions between dermatological nurses and dermatologists (n = 4). Triangulation of data, methods and analyses was performed. The quantitative data were analyzed by means of SPSS 11.5 for Windows. Categorical and ordinal variable were presented as frequency and percentage distributions, and medians, quartiles and arithmetic means were quoted. The interrelations between variables were presented as cross-tabulations, and Khi square test was used. The interviews were analyzed by methods of data-based content analysis. The more severe the child's atopic dermatitis was, the more the quality of life of the child and the family was impaired. The quality of life of the children was better than the quality of life of the families. The impact of the atopic dermatitis to the quality of life of the children was moderate and of the family severe. The children's quality of life was impaired most by itching and scratching. The need to participate in the treatment of the children's skin problems was the most important single factor that impaired the families' quality of life. The child's severe, long-term dermatitis and its treatment on a day-to-day basis were described as a desperate process. The knowledge that eczema is alleviated as the child grows older gave the families hope and helped them to cope. The avoidance of various foods and allergens and the opportunities to try different treatments raised hopes about the alleviation of eczema. On the other hand, however, these trials easily turned into desperate efforts to try any available alternative, which often wore out the mother or the whole family. Families did not receive adequate counselling or support when their quality of life was seriously compromised. The results of the study can be used when developing the public health care services to better meet the needs of families. / Tiivistelmä Tutkimuksen tarkoituksena on saada tietoa ihoatoopikkolasten (0–10 vuotta) ja heidän perheidensä arjesta. Tutkimuksen lähestymistapa on etnografinen. Erilaisia aineistoja kerättiin haastattelemalla, havainnoimalla ja kyselylomakkeilla. Perheiden (n = 7) haastattelut (n = 24) ja havainnoinnit (n = 24) tehtiin heidän kodeissaan. Perheiden arki heijastui haastattelutilanteisiin siten, että niissä ei aina ollut läsnä koko perhe, ja haastatteluun osallistujien toiveiden mukaan tapaamisia oli myös esimerkiksi ihotautien vuodeosastolla ja poliklinikalla. 5–10-vuotiaat lapset (n = 80) täyttivät itse tai vanhempiensa avustamana omaa elämänlaatuaan koskevan kyselylomakkeen. Alle 5-vuotiaiden lasten (n = 174) ja perheiden (n = 254) elämänlaatukyselyyn vastasivat vanhemmat. Lääkäri arvioi jokaisen tutkimukseen osallistuneen lapsen (n = 254) atooppisen ihottuman vaikeuden. Ammattilaisten näkökulman tutkimukseen toivat ihotautisairaanhoitajien ja -lääkäreiden kanssa käydyt keskustelut (n = 4). Tutkimuksessa käytetään aineisto-, menetelmä- ja analyysitriangulaatiota. Kvantitatiivinen aineisto analysoidaan SPSS 11.5 for Windows -ohjelmalla. Luokittelu- ja järjestysasteikollisia muuttujia kuvataan frekvenssi- ja %-jakaumilla, ja sijaintilukuina ovat mediaanit, kvartiilit ja aritmeettinen keskiarvo. Muuttujien yhteyksiä tarkastellaan ristiintaulukoimalla ja parametrittomana testinä on chi2-testi. Haastattelu- ja havainnointiaineisto analysoidaan aineistolähtöisellä sisällönanalyysillä. Mitä vaikeampi lapsen ihottuma oli, sitä enemmän se heikensi perheen ja lapsen elämänlaatua. Lasten elämänlaatu oli parempi kuin perheiden elämänlaatu. Atooppisen ihottuman vaikutus lasten elämänlaatuun oli kohtalainen ja perheiden elämänlaatuun huomattava. Lasten elämänlaatua heikensivät eniten kutina ja raapiminen. Lapsen hoidossa auttaminen oli tärkein perheen elämänlaatua heikentävä tekijä. Lapsen vaikeaa, pitkäaikaista ihottumaa ja sen päivästä toiseen jatkuvaa hoitamista kuvattiin ajoittain epätoivoiseksi. Toisaalta tieto, että ihottuma lievittyy lapsen kasvaessa, antoi toivoa ja auttoi perhettä jaksamaan. Perheet hankkivat ja saivat paljon ja monenlaista tietoa lapsen atooppisesta ihottumasta ja sen hoitamisesta, joten vanhemmat joutuivat suodattamaan ja puntaroimaan saamaansa tietoa oman lapsen tilanteeseen sopivaksi. Yhtäältä erilaisten ruokien tai ärsyttävien tekijöiden välttämiseen ja hoitovaihtoehtojen kokeilemiseen liittyi toivoa lapsen ihottuman lievittymisestä. Toisaalta kokeileminen saattoi kääntyä epätoivoiseksi tarttumiseksi jokaiseen tarjolla olevaan oljenkorteen, mikä puolestaan johti äidin tai koko perheen väsymiseen. Perheiden ohjauksessa ja tukemisessa oli puutteita, kun perheen elämänlaatu oli huomattavasti heikentynyt. Perheet käyttivät monipuolisesti terveydenhuollon palveluja, mutta ajoittain hoito koettiin pirstaleiseksi, ja hoitovastuu jäi perheen itsensä kannettavaksi. Tutkimustuloksia voidaan käyttää kehitettäessä terveydenhuoltopalveluja paremmin perheiden tarpeita vastaaviksi. Keskeistä on tunnistaa ne perheet, joiden elämänlaatu on huomattavasti heikentynyt lapsen atooppisen ihottuman vuoksi. Ihoatoopikkolapsen hoitaminen on moniammatillista yhteistyötä, jonka tekemistä yli ammattikunta- tai sektorirajojen on entisestään syytä tehostaa.

This master thesis focuses on atopic eczema in children and adolescents from a psychological perspective. The aim of this text is to describe and emphasize the psychological aspects of this disease and characterize the areas it may concern and affect. Regarding the structure, the thesis is divided into three parts. The introductory theoretical part is focused on a description of the explored subject-matter, the aim was to submit a comprehensive perspective on this disease and outline a relevant psychological basis for the empirical enquiry. The second empirical part is focused on the intrinsic aspects of the experience of this disease in children and adolescents. The quantitative research was designed to map out the specific phenomena, incidence of depressive symptoms and family upbringing style. The quantitative research is complemented by a qualitative inquiry with the aim to get further into depth of the issue by means of two case studies. These were focused on the overall experience related to the diagnosis of atopic eczema. The final part reflects acquired findings and the conclusive discussion summarizes the results of the exploratory assumptions including the limits and the possibilities of future psychological work with this disease. Keywords Atopic eczema, psychosomatic approach,...

Background: Birch pollen is an important outdoor allergen able to aggravate symptoms in atopic dermatitis (AD). Specific immunotherapy (SIT), an established procedure for allergic airway diseases, might also represent an attractive therapeutic option for the causal treatment of allergen-triggered cutaneous symptoms in these patients. Studies with house dust mite SIT have already shown beneficial effects in AD patients, whereas the safety and efficacy of SIT with birch pollen extract in AD patients have not been studied so far. The aim of this study was to evaluate for the first time the safety and efficacy of SIT with a depigmented polymerized birch pollen extract in AD patients. Methods: Fifty-five adult patients with moderate-to-severe AD and clinically relevant sensitization to birch pollen received SIT for 12 weeks. SIT was continued during birch pollen season. The assessment of safety, the total SCORAD value, and the Dermatology Life Quality Index (DLQI) were evaluated. Results: The median total SCORAD value was reduced by 34% (p < 0.001) during the course of treatment and the mean DLQI improved by 49% (p < 0.001) despite strong simultaneous birch pollen exposure. Eight patients (14.5%) developed systemic reactions and 19 patients (34.5%) developed local reactions which were of mild intensity in most cases. No patient discontinued the study prematurely due to adverse drug reactions. Coseasonal treatment was well tolerated. Conclusion: SIT with a depigmented polymerized birch pollen extract leads to significant improvement of the SCORAD value and the DLQI in patients suffering from moderate-to-severe AD sensitized to birch pollen. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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La régulation de l'homéostasie intestinale est de la plus haute importance en raison de la constante exposition de l'intestin aux antigènes alimentaires et à la flore commensale. La perturbation de la flore intestinale est souvent associée à diverses maladies telles que l'allergie, l'obésité et certaines maladies inflammatoires. La plupart des individus sont tolérant aux antigènes alimentaires et ne développe pas de réponse immunitaire sauf en cas de prédisposition génétique ou d'exposition à un environnement défavorable. La réponse allergique se caractérise par la production d'IgE stimulé par les lymphocytes Th2. Les symptômes allergiques sont très variés et affectent plusieurs parties de l'organisme. La plupart des travaux de recherche se sont focalisé jusqu'à présent sur le rôle des cellules de l'immunité adaptative dans le développement de l'allergie en sous-estimant le rôle majeur des cellules épithéliales et des cellules de l'immunité innée. L'objectif de ce projet est de comprendre comment les cellules épithéliales intestinales modulent la réponse immunitaire à distance vers la muqueuse pulmonaire ou la peau après stimulation allergique. L'ingestion de l'antigène associé à l'adjuvant de la toxine cholérique permet d'étudier la réponse allergique chez l'animal. Nous avons démontré sur ce modèle animal que l'absence de la kinase inhibitrice IKKb dans la voie de signalisation du facteur de transcription NF-kB altère la composition de la flore intestinal d'une part et transforme la réponse immunitaire inflammatoire au niveau pulmonaire et de la peau grâce à la présence d'IgA et de lymphocyte Th17 d'autre part. En adéquation avec les observations cliniques rapportées chez les patients allergiques (allergies alimentaires, asthme, dermatite atopique), nos résultats identifient IKKb dans la cellule épithéliale intestinale comme cible potentielle pour traiter les allergies alimentaires. De futurs efforts devront être faits pour développer de nouvelles stratégies thérapeutiques qui considèrent la muqueuse intestinale, la production d'IgA et l'importance des bactéries commensales dans le traitement des allergies. / Immune homeostasis is of paramount importance in the gastrointestinal tract, which is constantly exposed to ingested antigens and commensal microbiota. The gut microbiota can be perturbed by endogenous or exogenous factors and it is now established that microbial dysbiosis is associated with allergy, obesity, and inflammatory diseases. Ingestion of food antigens generally fails to promote brisk immune responses but rather results in a state of immune tolerance. However, aberrant immune responses can develop in individuals with a genetic predisposition. Food allergies are generally regarded as pathologic responses to food antigens mediated by excessive Th2 responses and antigen-specific IgE antibody responses. Clinical manifestations of food allergies are very broad and symptoms can affect different organs. While past research on allergy focused on the role of cells and molecules involved in adaptive immunity, epithelial cells lining the sites of antigen entry and innate immune responses have recently emerged as important players in allergy. This project was undertaken to understand the mechanisms employed by intestinal epithelial cells (IECs) to shape immune responses to allergens and influence allergic manifestations in distant mucosal sites such as the airways or the skin. Oral administration of food antigen with cholera toxin as adjuvant in experimental animals is a well-accepted model to study allergic sensitization to food antigens. Using this model, we show that a localized impairment of the canonical NF-κB pathway through deletion of IkB kinase (IKKβ) in IECs alters the gut microbiota during oral allergic sensitization and regulates the magnitude of allergic inflammatory responses at distant sites of the airway and the skin through enhancement of IgA Abs and Th17 responses. Consistent with the clinical observations linking atopic diseases (food allergy, allergic asthma, atopic dermatitis), our results identify IKKβ in IECs as a potential therapeutic target for treatment of food allergies and subsequent disease. They also suggest that future efforts for controlling allergic responses in the airways and the skin could include strategies that use the gut microbiota and promote IgA Ab responses and prevent IL-17 responses.