Dose-response effect of steroid hormones on Gfi1 and U2af1l4 gene expression in T lymphocytes at different stages of differentiation

The alternative splicing of the Ptprc gene is a key event in memory T-cell differentiation. This gene encodes a transmembrane tyrosine phosphatase CD45. One of the potential mechanisms of alternative splicing regulation is based on the antagonistic effects of a U2AF26 auxiliary splicing factor and G...

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Bibliographic Details
Published in:Molecular biology (New York) 2013-07, Vol.47 (4), p.572-580
Main Authors: Litvinova, L. S., Mazunin, I. O., Gutsol, A. A., Sokhonevich, N. A., Khaziakhmatova, O. G., Kofanova, K. A.
Format: Article
Language:English
Subjects:
Antigens
Biochemistry
Biomedical and Life Sciences
Cell Molecular Biology
Gene expression
Hormones
Human Genetics
Life Sciences
Lymphocytes
Proteins
T cell receptors
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Summary:The alternative splicing of the Ptprc gene is a key event in memory T-cell differentiation. This gene encodes a transmembrane tyrosine phosphatase CD45. One of the potential mechanisms of alternative splicing regulation is based on the antagonistic effects of a U2AF26 auxiliary splicing factor and Gfi1 transcription factor. These two proteins regulate antigen-dependent T-cell activation. We have shown that steroid hormones have different effects on the regulation of U2af1l4 and Gfi1 transcription in dissimilar stages of the differentiation of a cell culture subjected to antigen-independent stimulation. Low concentrations of glucocorticoid (Dex) and female sex hormone (Est) can activate expression of U2af1l4 in restimulated cells that probably induce the formation of isoforms of the terminal CD45 receptor, whereas high doses of hormones inhibit the process. Under the same conditions, in a wide range of concentrations (10 −5 –10 −7 M) and Est (10 −6 and 10 −7 M), Dex activates U2af1l4 gene expression, which probably leads to the formation of surrogate memory T cells. The dose-dependent effect of testosterone (Test) has the opposite effect of Est and Dex on primed (CD45RO+) and naive (CD45RA+) lymphocytes. The role of steroid hormones in memory T-cell differentiation under antigen-independent stimulation conditions is of great interest for the understanding of chronic hormonal and immune disbalance mechanisms.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893313040092