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Published on: June 9, 2023
Shared dependence on the DNA-binding factor TOX for the development of lymphoid tissue-inducer cell and NK cell
Parinaz Aliahmad1, Brian de la Torre, Jonathan Kaye
1Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Abstract:
TOX is a DNA-binding factor required for development of CD4(+) T cells, natural killer T cells and regulatory T cells. Here we document that both natural killer (NK) cell development and lymphoid tissue organogenesis were also inhibited in the absence of TOX. We found that the development of lymphoid tissue-inducer cells, a rare subset of specialized cells that has an integral role in lymphoid tissue organogenesis, required TOX. Tox was upregulated considerably in immature NK cells in the bone marrow, consistent with the loss of mature NK cells in the absence of this nuclear protein. Thus, many cell lineages of the immune system share a TOX-dependent step for development.
Insights
The transcription factor TOX is essential for the development of several immune cell types, including T cells and natural killer (NK) cells. Its absence impairs both immune cell maturation and the formation of lymphoid tissues.
Area of Science:
- Immunology
- Developmental Biology
Background:
- TOX is a DNA-binding factor known to be crucial for the development of CD4(+) T cells, natural killer T cells, and regulatory T cells.
- The precise role of TOX in broader immune system development and organogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the role of TOX in natural killer (NK) cell development and lymphoid tissue organogenesis.
- To identify specific cell types and developmental stages dependent on TOX.
Main Methods:
- Analysis of mice lacking the TOX gene.
- Flow cytometry to assess immune cell populations.
- Histological examination of lymphoid tissues.
Main Results:
- Absence of TOX significantly inhibited NK cell development and lymphoid tissue organogenesis.
- Development of lymphoid tissue-inducer cells, critical for organogenesis, was dependent on TOX.
- Tox expression was upregulated in immature NK cells, correlating with the loss of mature NK cells in TOX-deficient mice.
Conclusions:
- TOX plays a vital role in NK cell development and lymphoid tissue formation.
- Lymphoid tissue-inducer cell development is a TOX-dependent process.
- Multiple immune cell lineages share a common TOX-dependent developmental pathway.
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