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Importance of cAMP levels in dendritic cells in directing CD4⁺ T cell differentiation /

Abstract

Atopic March, a phenomenon that has surfaced during the 20th century (2) describes the progression of atopic disorders; atopic dermatitis in infants to allergic rhinitis and asthma in children. The frequency of this progression has increased in the recent decades. Atopic disease, which include allergic asthma is complex and is strongly influenced by both genetic and environmental factors. The word "Atopic" is used to describe the production of IgE. Therefore the approaches to understanding atopic diseases have centered on mechanisms in the adaptive immune system, often emphasizing the Th1- Th2 paradigm. However, recently many studies have indicated the importance of dendritic cells in CD4⁺ T cell differentiation. It is still very unclear in how dendritic cells directly influence CD4⁺ T cell differentiation to distinct subgroups, such as TH2 cells. Many studies have indicated the importance of cAMP levels in CD4⁺ T cell differentiation. Since dendritic cells are important in CD4⁺ T cell differentiation, we have developed a mice strain (Gnas[Delta]CD¹¹c mice) with a deletion of Gnas gene specifically in CD11c⁺ cells, which results in decreased cAMP levels. The decrease cAMP in dendritic cells directed Th2 differentiation. Observing the signal pathway of cAMP in dendritic cells we have found that it goes through the PKA pathway and G[alpha]i activation was found to be a key regulator of Th2 differentiation

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