Medizinische Universität Graz - Research portal
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SHR Neuro Cancer Cardio Lipid Metab Microb
Orola, MJ; Tizian, C; Zhu, C; Andersen, L; Gülich, AF; Alteneder, M; Stojakovic, T; Wiedermann, U; Trauner, M; Ellmeier, W; Sakaguchi, S.
The zinc-finger transcription factor MAZR regulates iNKT cell subset differentiation.
Cell Mol Life Sci. 2019; 76(21):4391-4404
Doi: 10.1007/s00018-019-03119-z
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- Co-authors Med Uni Graz
- Stojakovic Tatjana
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Differentiation - genetics
- Cell Differentiation - immunology
- Cells, Cultured -
- Gene Expression Regulation -
- Lymphocyte Subsets - physiology
- Mice -
- Mice, Inbred C57BL -
- Mice, Transgenic -
- Natural Killer T-Cells - classification
- Natural Killer T-Cells - physiology
- Neoplasm Proteins - physiology
- Repressor Proteins - physiology
- Transcription Factors - physiology
- Zinc Fingers - physiology
- Find related publications in this database (Keywords)
- iNKT cell subset differentiation
- iNKT cell function
- Transcriptional regulation
- PATZ1/MAZR