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Front. Immunol. | doi: 10.3389/fimmu.2018.01482

The Transcription Factor Zfx Regulates Peripheral T Cell Self-Renewal and Proliferation.

 Matthew Smith-Raska1*, Teresita Arenzana2, Louise D'Cruz3, Alireza Khodadadi-Jamayran4, Aristotelis Tsirigos4,  Ananda Goldrath5 and  Boris Reizis4
  • 1Newborn Medicine, Boston Children's Hospital, Harvard University, United States
  • 2Genentech, Inc., United States
  • 3Department of Immunology, University of Pittsburgh, United States
  • 4Department of Pathology, New York University, United States
  • 5Division of Biological Sciences, University of California, San Diego, United States

Peripheral T lymphocytes share many functional properties with hematopoietic stem cells (HSCs), including long-term maintenance, quiescence, and latent proliferative potential. In addition, peripheral T cells retain the capacity for further differentiation into a variety of subsets, much like HSCs. While the similarities between T cells and HSC has long been hypothesized, the potential common genetic regulation of HSCs and T cells has not been widely explored. We have studied the T cell-intrinsic role of Zfx, a transcription factor specifically required for HSC maintenance. We report that T cell-specific deletion of Zfx caused age-dependent depletion of naïve peripheral T cells. Zfx-deficient T cells also failed to undergo homeostatic proliferation in a lymphopenic environment, and showed impaired antigen-specific expansion and memory response. In addition, the invariant natural killer T cell (iNKT) cell compartment was severely reduced. RNA-Seq analysis revealed that the most dysregulated genes in Zfx-deficient T cells were similar to those observed in Zfx-deficient HSC and B cells. These studies identify Zfx as an important regulator of peripheral T cell maintenance and expansion, and highlight the common molecular basis of HSC and lymphocyte homeostasis.

Keywords: T cell self-renewal, T cell homeostasis, homeostatic proliferation, hematopoietic stem cell, T cell stress response

Received: 15 Mar 2018; Accepted: 14 Jun 2018.

Edited by:

Rene De Waal Malefyt, Merck (United States), United States

Reviewed by:

Ju Qiu, Shanghai Institutes for Biological Sciences (CAS), China
Bianca Blom, Academic Medical Center (AMC), Netherlands  

Copyright: © 2018 Smith-Raska, Arenzana, D'Cruz, Khodadadi-Jamayran, Tsirigos, Goldrath and Reizis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Matthew Smith-Raska, Boston Children's Hospital, Harvard University, Newborn Medicine, Boston, 02115, MA, United States, matt.r.smith.raska@gmail.com