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Mediators of Inflammation
Volume 2015, Article ID 243868, 7 pages
Review Article

The Role of TOX in the Development of Innate Lymphoid Cells

1Research Division of Immunology, Departments of Biomedical Sciences and Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
2Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA

Received 8 July 2015; Accepted 27 September 2015

Academic Editor: Carolina T. Piñeiro

Copyright © 2015 Corey R. Seehus and Jonathan Kaye. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.