The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment
Xiao He,Xi He,Vibhuti P. Dave,Yi Zhang,Xiang Hua,Emmanuelle Nicolas,Weihong Xu,Bruce A. Roe,Dietmar J. Kappes +8 more
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TLDR
It is shown that a point mutation in the zinc finger transcription factor Th-POK (T-helper-inducing POZ/Krüppel-like factor) is responsible for redirection of class-II-restricted thymocytes to the CD8 lineage in HD mice, indicating that Th- POK is a master regulator of lineage commitment.Abstract:
Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively, indicating that the process is carefully regulated. Although intensively studied owing to its importance in determining the composition of the mature T-cell compartment and as a general model of binary lineage decisions, the underlying molecular pathways remain obscure. We have previously reported a spontaneous mouse mutant (HD (helper deficient) mice) in which lineage commitment is specifically perturbed without affecting positive selection. Here we show that a point mutation in the zinc finger transcription factor Th-POK (T-helper-inducing POZ/Kruppel-like factor) is responsible for redirection of class-II-restricted thymocytes to the CD8 lineage in HD mice. Furthermore, we demonstrate that constitutive expression of this factor during thymic development leads to redirection of class-I-restricted thymocytes to the CD4 lineage, indicating that Th-POK is a master regulator of lineage commitment.read more
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Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
TL;DR: The authors showed that CD4+CD25+ cells contribute to maintaining self-tolerance by downregulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage.
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The Transcription Factor PLZF Directs the Effector Program of the NKT Cell Lineage
Adam K. Savage,Michael G. Constantinides,Jin Han,Damien Picard,Emmanuel Martin,Bofeng Li,Olivier Lantz,Albert Bendelac +7 more
TL;DR: PLZF is a transcriptional signature of NKT cells that directs their innate-like effector differentiation during thymic development and is exquisitely specific to CD1d-restricted N KT cells and human MR1-specific MAIT cells.
Journal ArticleDOI
Foxp3 Transcription-Factor-Dependent and -Independent Regulation of the Regulatory T Cell Transcriptional Signature
Jonathan A. Hill,Markus Feuerer,Kaley Tash,Sokol Haxhinasto,Jasmine Perez,Rachel D. Melamed,Diane Mathis,Christophe Benoist +7 more
TL;DR: A cross-sectional analysis of the Treg cell signature in Treg-like cells generated under a number of conditions is performed to delineate the elements that can be ascribed to T cell activation, interleukin-2, transforming growth factor-beta (TGF-beta) signaling, or Foxp3 itself.
Journal ArticleDOI
The BTB–zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions
Damian Kovalovsky,Olisambu U. Uche,Sonia Eladad,Robin M. Hobbs,Robin M. Hobbs,Woelsung Yi,Eric S. Alonzo,Kevin Chua,Maggie Eidson,Hye-Jung Kim,Jin S. Im,Pier Paolo Pandolfi,Pier Paolo Pandolfi,Derek B. Sant'Angelo,Derek B. Sant'Angelo,Derek B. Sant'Angelo +15 more
TL;DR: It is shown here that iNKT cells specifically expressed the BTB–zinc finger transcriptional regulator PLZF, which is an iN KT cell–specific transcription factor that is necessary for full functionality.
Journal ArticleDOI
T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer.
Bradley S. Cobb,Tatyana B. Nesterova,E. Thompson,Arnulf Hertweck,Eric D. O'Connor,Jonathan Godwin,Christopher B. Wilson,Neil Brockdorff,Amanda G. Fisher,Stephen T. Smale,Stephen T. Smale,Matthias Merkenschlager +11 more
TL;DR: In developing thymocytes, Dicer was not required for the maintenance of transcriptional silencing at pericentromeric satellite sequences, so it may have limited impact on the implementation of some lineage-specific gene expression programs.
References
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The Transcription Factor GATA-3 Is Necessary and Sufficient for Th2 Cytokine Gene Expression in CD4 T Cells
TL;DR: In transgenic mice, elevated GATA-3 in CD4 T cells caused Th2 cytokine gene expression in developing Th1 cells, indicating that Gata-3 is necessary and sufficient for Th2inflammatory gene expression.
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Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4 + 8 + thymocytes
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Journal ArticleDOI
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John C. Pui,David Allman,Lanwei Xu,Susan DeRocco,Fredrick G. Karnell,Sonia Bakkour,Julia Y Lee,Tom Kadesch,Richard R. Hardy,Jon C. Aster,Warren S. Pear +10 more
TL;DR: The results suggest that Notch1 provides a key regulatory signal in determining T lymphoid versus B lymphoid lineage decisions, possibly by influencing lineage commitment from a common lymphoid progenitor cell.
Journal ArticleDOI
Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells
Shih-Feng Tsai,David I. K. Martin,David I. K. Martin,Leonard I. Zon,Leonard I. Zon,Alan D. D'Andrea,Alan D. D'Andrea,Gordon G. Wong,Stuart H. Orkin,Stuart H. Orkin +9 more
TL;DR: Genes expressed in erythroid cells contain binding sites for a cell-specific factor believed to be an important regulator for this haematopoietic lineage, and complementary DNA encoding the murine protein is identified using high-level transient expression in mammalian cells.
Journal ArticleDOI
Differential Requirements for Runx Proteins in CD4 Repression and Epigenetic Silencing during T Lymphocyte Development
Ichiro Taniuchi,Motomi Osato,Takeshi Egawa,Mary Jean Sunshine,Suk Chul Bae,Toshihisa Komori,Yoshiaki Ito,Dan R. Littman +7 more
TL;DR: It is shown here that binding sites for Runt domain transcription factors are essential for CD4 silencer function at both stages, and that different Runx family members are required to fulfill unique functions at each stage.