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Regulation of FOXP3 Expression in Blood Cells in Response to All-Trans-Retinoic Acid, Interleukin 2 and Transforming Growth Factor β
: Received: 11 December 2018 / Approved: 12 December 2018 / Online: 12 December 2018 (15:51:17 CET)
A peer-reviewed article of this Preprint also exists.
Journal reference: Developmental & Comparative Immunology 2019, 96, 18-26
FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage
blood cells; differentiation; myeloid leukemia; monocytes; lymphocytes; transcription factors; all-trans-retinoic acid; interleukin 2; transforming growth factor β
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