TOX2 regulates human natural killer cell development by controlling T-BET expression
| Autor: | Barbara Rooney, Jim Houston, Ying Li, Wai-Hang Leung, Queenie P. Vong, Martha Holladay, Robert A.J. Oostendorp, Wing Leung |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Transcription
Genetic Cellular differentiation Immunology chemical and pharmacologic phenomena Antigens CD34 Biology Biochemistry Natural killer cell Interleukin 21 Mice Mice Inbred NOD HMGB Proteins medicine Animals Humans Gene Silencing Lymphocytes Transcription factor Immunobiology Oligonucleotide Array Sequence Analysis Lymphokine-activated killer cell Lentivirus Gene Expression Regulation Developmental hemic and immune systems Cell Differentiation Cell Biology Hematology Fetal Blood Molecular biology Protein Structure Tertiary Killer Cells Natural Thymocyte TOX2 medicine.anatomical_structure HEK293 Cells Liver Interleukin 12 T-Box Domain Proteins Protein Binding |
| Popis: | Thymocyte selection-associated high mobility group box protein family member 2 (TOX2) is a transcription factor belonging to the TOX family that shares a highly conserved high mobility group DNA-binding domain with the other TOX members. Although TOX1 has been shown to be an essential regulator of T-cell and natural killer (NK) cell differentiation in mice, little is known about the roles of the other TOX family members in lymphocyte development, particularly in humans. In this study, we found that TOX2 was preferentially expressed in mature human NK cells (mNK) and was upregulated during in vitro differentiation of NK cells from human umbilical cord blood (UCB)-derived CD34(+) cells. Gene silencing of TOX2 intrinsically hindered the transition between early developmental stages of NK cells, whereas overexpression of TOX2 enhanced the development of mNK cells from UCB CD34(+) cells. We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). Overexpression of T-BET rescued the TOX2 knockdown phenotypes. Given the essential function of T-BET in NK cell differentiation, TOX2 therefore plays a crucial role in controlling normal NK cell development by acting upstream of TBX21 transcriptional regulation. |
| Databáze: | OpenAIRE |
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