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Publication : The zinc-finger transcription factor MAZR regulates iNKT cell subset differentiation.

First Author  Orola MJ Year  2019
Journal  Cell Mol Life Sci Volume  76
Issue  21 Pages  4391-4404
PubMed ID  31065747 Mgi Jnum  J:289696
Mgi Id  MGI:6434605 Doi  10.1007/s00018-019-03119-z
Citation  Orola MJ, et al. (2019) The zinc-finger transcription factor MAZR regulates iNKT cell subset differentiation. Cell Mol Life Sci 76(21):4391-4404
abstractText  Invariant natural killer T (iNKT) cells represent a subgroup of innate-like T cells and play an important role in immune responses against certain pathogens. In addition, they have been linked to autoimmunity and antitumor immunity. iNKT cells consist of several subsets with distinct functions; however, the transcriptional networks controlling iNKT subset differentiation are still not fully characterized. Myc-associated zinc-finger-related factor (MAZR, also known as PATZ1) is an essential transcription factor for CD8(+) lineage differentiation of conventional T cells. Here, we show that MAZR plays an important role in iNKT cells. T-cell lineage-specific deletion of MAZR resulted in an iNKT cell-intrinsic defect that led to an increase in iNKT2 cell numbers, concurrent with a reduction in iNKT1 and iNKT17 cells. Consistent with the alteration in the subset distribution, deletion of MAZR also resulted in an increase in the percentage of IL-4-producing cells. Moreover, MAZR-deficient iNKT cells displayed an enhanced expression of Erg2 and ThPOK, key factors for iNKT cell generation and subset differentiation, indicating that MAZR controls iNKT cell development through fine-tuning of their expression levels. Taken together, our study identified MAZR as an essential transcription factor regulating iNKT cell subset differentiation and effector function.
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