Shared dependence on the DNA-binding factor TOX for the development of lymphoid tissue–inducer cell and NK cell lineages

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.

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Figure 1: Absence of lymph nodes from Tox−/− mice.
Figure 2: Defect in the formation of lymph node structures in Tox−/− mice.
Figure 3: TOX is required for the development of LTi cells.
Figure 4: Impaired development of NK cells in the absence of TOX.
Figure 5: Defect in NK cell development in the absence of TOX is cell intrinsic.
Figure 6: Expression of Tox but not of Id2 can restore NK cell development.

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Acknowledgements

We thank K. Wawrowsky for assistance with confocal microscopy; P. Lin for cell sorting; A. Kadavallore for technical assistance; and A. Seksenyan for critical reading of this manuscript. Supported by the National Institutes of Health (R01AI054977 to J.K.).

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P.A. and B.d.l.T. did experiments; and P.A. and J.K. devised the experimental design, analyzed data and wrote the manuscript.

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Correspondence to Jonathan Kaye.

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The authors declare no competing financial interests.

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Aliahmad, P., de la Torre, B. & Kaye, J. Shared dependence on the DNA-binding factor TOX for the development of lymphoid tissue–inducer cell and NK cell lineages. Nat Immunol 11, 945–952 (2010). https://doi.org/10.1038/ni.1930

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