Understanding the Metabolic Regulation of the Transcription Factor c-Maf in Human CD4+ T Cells
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Saudi Digital Library
Abstract
c-Maf is a member of the Activator Protein-1 transcription factor superfamily and has been
characterized as a master regulator of IL-10 expression in T cells. It plays key roles in the differentiation and function of various effector T cell lineages. In purified human CD4+ T cells,
IL-10 has been proven to be metabolically regulated by cellular metabolism, as was c-Maf.
Considering the above, we aimed to characterize the way in which c-Maf expression is
regulated by the cholesterol biosynthesis pathway, particularly focusing on the stimulation
signals that would upregulate the transcription factor and on the effects the perturbation of
the cholesterol pathway would have on c-Maf. Through analyses by quantitative real-time
PCR and flow cytometry, it was proven that stimulation via anti-CD3 and recombinant human
interleukin-2 upregulated c-Maf expression. Inhibition of the cholesterol biosynthesis
pathway with 25-hydroxycholesterol significantly decreased the levels of c-Maf, both at the protein and mRNA level and analysing the CD4+ T cells post inhibition via flow cytometry
revealed decreased staining for phosphorylated STAT5. Introducing cholesterol to our cell
cultures restored the pathway back to homeostasis and regained c-Maf expression, implying
a link between sterol metabolism and the regulation of c-Maf. Our data also reveals IL-2 to
be crucial in regulating c-Maf via its signalling through the IL-2 receptor and phosphorylated
STAT5.