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Mast cells are key players in type I hypersensitivity reactions in humans and mice and their activity has to be tightly controlled. Previous studies implicated the transcription factor MAZR in the regulation of mast cell function. To study the role of MAZR in mast cells, we generated a conditional  Mazr  allele and crossed  Mazr   F/F  mice with the  Vav-iCre  deleter strain, which is active in all hematopoietic cells. MAZR-null BM-derived mast cells (BMMC) were phenotypically indistinguishable from wild-type BMMCs, although the numbers of IL-3 generated  Mazr    F/F    Vav-iCre  BMMCs were reduced in comparison to  Mazr    F/F   BMMCs, showing that MAZR is required for the efficient generation of BMMC  in vitro . A gene expression analysis revealed that MAZR-deficiency resulted in the dysregulation of 128 genes, with more genes up- than down-regulated in the absence of MAZR, indicating that MAZR acts as a transcriptional repressor in mast cells. Among the up-regulated genes were the chemokines  Ccl5 ,  Cxcl10 ,  Cxcl12 , the chemokine receptor  Ccr5  and the cytokine  IL18 , suggesting an immunoregulatory role for MAZR in mast cells. Enforced expression of MAZR in mature  Mazr -deficient BMMCs rescued the altered expression pattern of some genes tested, suggesting direct regulation of these genes by MAZR. Upon FcεRI stimulation,  Mazr  expression was transiently down-regulated in BMMCs. However, early and late effector functions in response to FcεRI-mediated stimulation were not impaired in the absence of MAZR, with the exception of IL-6, which was slightly decreased. Taken together, out data indicate that MAZR preferentially acts as a transcriptional repressor in mast cells, however MAZR plays only a minor role in the transcriptional networks that regulate early and late effector functions in mast cells in response to FcεRI stimulation.

plos one

The Transcription Factor MAZR Preferentially Acts as a Transcriptional Repressor in Mast Cells and Plays a Minor Role in the Regulation of Effector Functions in Response to FcεRI Stimulation