Mast cell transcription factors--regulators of cell fate and phenotype

Abstract

Transcription factors have a key role in mast cell differentiation and response of differentiated mast cells to external stimuli. During differentiation of progenitor cells to mast cells, a role for different GATA transcription factors in combination with PU.1 expression and downregulation of C/EBPα has been described. Notch pathway has been proposed to have a role in mast cell development. The microphthalmia-associated transcription factor expression is upregulated in later stages of mast cells differentiation, but it is not expressed in the closely related basophiles. In differentiated mast cells, there is a role for transcription factors both in determining the specific mast cell phenotype and in the response to immune stimuli such as IgE-Ag. A large number of transcription factors, including AP-1 family proteins, microphthalmia-associated transcription factor and STAT5, are modulated by these stimuli. These transcription factors and related protein modulators form a complex transcription factor network. They can form stimuli regulated specific heterodimers and common inhibitors can move from one protein to another. Transcription factors are the key regulators of mast cell physiology. Modulation of key transcription by such means as the therapeutic siRNA may hopefully allow us to modulate mast cell function, obtaining clinical benefit in a variety of diseases. This article is part of a Special Issue entitled: Mast cells in inflammation.