Abstract
FoxP3 is a transcription factor essential for 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 expression of genes regulated by 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 expression of FOXP3 gene in normal and leukemic myeloid cells. Our results indicate that signaling pathways which are used at the late steps of T cell differentiation, are also active in the cells of myeloid lineage.
Highlights
Blood cells develop in bone marrow in a process called hematopoiesis
According to the branching tree model of hematopoiesis, there are two types of pluripotent progenitors, common lymphoid progenitors (CLPs) which give rise to natural killers (NK), B and T cells, and common myeloid progenitors (CMPs) which further differentiate into platelets, erythrocytes, granulocytes, monocytes and mast cells
Expression of wide array of genes connected with blood differentiation in HL60 cells exposed to 1,25D or to all-trans-retinoic acid (ATRA)
Summary
Blood cells develop in bone marrow in a process called hematopoiesis. All blood cells originate from multipotent hematopoietic stem cells (HSCs) which after division generate daughter stem cells and pluripotent progenitor cells [1]. According to the branching tree model of hematopoiesis, there are two types of pluripotent progenitors, common lymphoid progenitors (CLPs) which give rise to natural killers (NK), B and T cells, and common myeloid progenitors (CMPs) which further differentiate into platelets, erythrocytes, granulocytes, monocytes and mast cells. The experiments have revealed that progenitors of B cells and monocytes [3, 4], as well as those of T cells and monocytes, are closely related [5, 6]. These data indicate that a sharp distinction between lymphoid and myeloid differentiation pathways does not exist [7]. A pairwise relationships model of hematopoiesis has been proposed according to which HSCs can reach a specific cell fate through more than one type of intermediate progenitors [8]
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