A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response.
Allergies involve a state of immediate hypersensitivity to antigens, including food proteins. The mechanism underlying the initiation and development of allergic responses involves IL-4 that directly induces the differentiation of committed effector Th2 lymphocytes. Although it is clear that Th2 responses play a pivotal role in the development of allergic responses, it remains unclear which mechanisms are involved in the development of the intestinal damages observed in food allergy. Accordingly, this work aimed to study the role of Th2/IL-4-dependent responses in the development of food allergy and intestinal pathology. C57BL/6 wild-type (WT) and IL-4-/- mice were sensitized with peanut proteins, challenged with peanut seeds, and followed for the development of food allergy and intestinal inflammation. Results demonstrated that exposure to peanut seeds led to weight loss in WT but not in IL-4-/- mice that preserved gut integrity with no signs of mucosal inflammation. These animals presented increased levels of IgG2a in sera, suggesting a role for allergic antibodies in the pathogenesis of WT animals. Most importantly, results also showed that lack of IL-4 modulated gut mucosal response in food allergy through diminished expression of TNF-alpha mRNA, increased Th1 IFN-gamma, IL-12p40, regulatory cytokines, and Foxp3, demonstrating their relevance in the control of allergic inflammatory processes, especially in the intestine. Finally, this study highlighted some of the complex mechanisms involved in the pathogenesis of allergic responses to food antigens in the gut, thereby providing valuable tools for directing novel therapeutic or preventive strategies to the control of allergic enteropathy.
Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4 þ leukocytes in the inflammatory infiltrate on days þ 7 and þ 14 and of CD8 þ cells on day þ 7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that highdose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.
Introdução: A aplicação do telediagnóstico em dermatologia pode apresentar diversos benefícios como a redução do tempo de espera para consultas com especialistas focais, triagem de doenças graves - principalmente neoplasias - e educação permanente de profissionais. Objetivo: Relatar a experiência da implantação do serviço de teledermatologia no município de Florianópolis - Santa Catarina - e o impacto inicial do processo no acesso e qualificação da assistência aos pacientes com afecções dermatológicas. Métodos: Estudo observacional, transversal e descritivo. Foram utilizados dados do sistema de prontuário eletrônico municipal, base de dados da plataforma Telessaúde-SC e documentos públicos institucionais da Secretaria Municipal de Saúde de Florianópolis entre os anos de 2013 e 2017. Resultados: O serviço de teledermatologia foi implementado no município de Florianópolis em 2015, por meio da adesão ao Sistema Integrado Catarinense de Telemedicina e Telessaúde. O processo de adequação ocorreu por meio da aquisição de equipamentos, adaptações na infraestrutura e capacitações de servidores. No período analisado, verificou-se redução de 52,6% na taxa de encaminhamentos para dermatologia, com expressiva diminuição no tempo de espera para consulta de cerca de 3 anos, em 2013 e 2014, para 20 dias em 2017. Nota-se tendência à qualificação dos encaminhamentos ao serviço, com redução nos laudos emitidos com classificação azul, manejados na APS, e aumento de laudos com classificação amarela, referenciados para dermatologia. Conclusão: A implantação da teledermatologia em Florianópolis representou um grande avanço para o processo de integração entre a Atenção Primária à Saúde e Atenção Especializada, contribuindo para a redução nas filas de espera e na qualificação dos encaminhamentos, com potencial para o aprimoramento da coordenação do cuidado e educação continuada dos profissionais.
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