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Published May 2018 | Published
Journal Article Open

Cytokines, Transcription Factors, and the Initiation of T-Cell Development

Abstract

Multipotent blood progenitor cells migrate into the thymus and initiate the T-cell differentiation program. T-cell progenitor cells gradually acquire T-cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T-cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals. Together with Notch or pre-T-cell-receptor (TCR) signaling, cytokines always control proliferation, survival, and differentiation of early T cells, but little is known regarding their cross talk with transcription factors. However, recent results suggest ways that cytokines expressed in distinct intrathymic niches can specifically modulate key transcription factors. This review discusses how stage-specific roles of cytokines and transcription factors can jointly guide development of early T cells.

Additional Information

© 2018 Cold Spring Harbor Laboratory Press. The Authors acknowledge that six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, http://creativecommons.org/licenses/by-nc/4.0/). Published online July 17, 2017. The authors thank Jonas Ungerbäck and other members of the Rothenberg group for valuable discussions and advice and for sharing data before publication. Support was provided by the Manpei Suzuki Diabetes Foundation to H.H., the Albert Billings Ruddock Professorship to E.V.R., and grants from the United States Public Health Service (USPHS) to the Rothenberg Laboratory (R01 AI95943 and R01 HD76915).

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