Prostaglandin E2 (PGE2) is one of the main mediators involved in the differentiation and/or expansion of T helper (Th) Th1 and Th17 cells in inflammatory disorders models, such as experimental autoimmune encephalomyelitis (EAE) and experimental models of colitis. This prostanoid plays an important role in the differentiation of T lymphocyte subpopulations, through PGE2 receptors, EP2 and EP4 via activation of cAMP /PKA and PI3K. Inhibition of PGE2, or blockage of it's EP receptors leads to inhibition of the clinical course of these inflammatory diseases. The coexistence of Th1 and Th17 lymphocytes, as well as the presence of Th17 cells producing IFN-³ suggests the possible plasticity of these sub-populations of lymphocytes in models of inflammatory disorders. However, until now, there are no reports in the literature that the presence of PGE2 could favor the plasticity of Th17 lymphocytes into Th1. Recently data obtained by our research group showed that Th17 cells cultured in Th1 polarizing conditions in the presence of PGE2 exhibited an increase in the plasticity of Th17 to Th1 limphocytes. However, the mechanisms by which this lipid mediator could act on this plasticity has not been investigated yet. Therefore, the hypothesis of this project is that in a polarizing microenvironment to Th1 cells, PGE2 acts through EP2/EP4 receptors in Th17 cells, incitationg a signaling cascade through activation of cAMP/PKA or EPAC or PI3K-AKT, which results in a plasticity increase of Th17 cells to Th1.
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