scholarly journals A Chemical Biology Toolbox for the Study of Protein Methyltransferases and Epigenetic Signaling

2018 ◽  
Author(s):  
Sebastian Scheer ◽  
Suzanne Ackloo ◽  
Tiago S. Medina ◽  
Matthieu Schapira ◽  
Fengling Li ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Chemical Probes ◽  
Th1 Cell ◽  
Regulatory Enzymes ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Protein Methyltransferases

SUMMARYProtein methyltransferases (PMTs) comprise a major class of epigenetic regulatory enzymes with therapeutic relevance. Here we present a collection of chemical probes and associated reagents and data to elucidate the function of human and murine PMTs in cellular studies. Our collection provides inhibitors and antagonists that together modulate most of the key regulatory methylation marks on histones H3 and H4, providing an important resource for modulating cellular epigenomes. We describe a comprehensive and comparative characterization of the probe collection with respect to their potency, selectivity, and mode of inhibition. We demonstrate the utility of this collection in CD4+ T cell differentiation assays revealing the remarkable potential of individual probes to alter multiple T cell subpopulations with important implications for T cell-mediated processes such as inflammation and immuno-oncology. In particular, we demonstrate a role for DOT1L in limiting Th1 cell differentiation and maintaining lineage integrity.

scholarly journals Functional and Clinical Characterization of Tumor-Infiltrating T Cell Subpopulations in Hepatocellular Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Jianguo Li ◽  
Jin Zhou ◽  
Shuangshuang Kai ◽  
Can Wang ◽  
Daijun Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

scholarly journals Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells’ Differentiation and Function in Induction of Colitis

2019 ◽  
Vol 25 (9) ◽  
pp. 1450-1461 ◽  
Author(s):  
Liang Chen ◽  
Mingming Sun ◽  
Wei Wu ◽  
Wenjing Yang ◽  
Xiangsheng Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Gut Microbiota ◽  
Th17 Cell ◽  
Cell Development ◽  
Cell Polarization ◽  
T Cell Differentiation ◽  
Th1 Cell ◽  
And Function

Abstract Background How the gut microbiota regulates intestinal homeostasis is not completely clear. Gut microbiota metabolite short-chain fatty acids (SCFAs) have been reported to regulate T-cell differentiation. However, the mechanisms underlying SCFA regulation of T-cell differentiation and function remain to be investigated. Methods CBir1, an immunodominant microbiota antigen, transgenic T cells were treated with butyrate under various T-cell polarization conditions to investigate butyrate regulation of T-cell differentiation and the mechanism involved. Transfer of butyrate-treated CBir T cells into Rag1-/- mice was performed to study the in vivo role of such T cells in inducing colitis. Results Although butyrate promoted Th1 cell development by promoting IFN-γ and T-bet expression, it inhibited Th17 cell development by suppressing IL-17, Rorα, and Rorγt expression. Interestingly, butyrate upregulated IL-10 production in T cells both under Th1 and Th17 cell conditions. Furthermore, butyrate induced T-cell B-lymphocyte-induced maturation protein 1 (Blimp1) expression, and deficiency of Blimp1 in T cells impaired the butyrate upregulation of IL-10 production, indicating that butyrate promotes T-cell IL-10 production at least partially through Blimp1. Rag1-/- mice transferred with butyrate-treated T cells demonstrated less severe colitis, compared with transfer of untreated T cells, and administration of anti-IL-10R antibody exacerbated colitis development in Rag-/- mice that had received butyrate-treated T cells. Mechanistically, the effects of butyrate on the development of Th1 cells was through inhibition of histone deacetylase but was independent of GPR43. Conclusions These data indicate that butyrate controls the capacity of T cells in the induction of colitis by differentially regulating Th1 and Th17 cell differentiation and promoting IL-10 production, providing insights into butyrate as a potential therapeutic for the treatment of inflammatory bowel disease.

Characterization of multiple alleles of the T-cell differentiation marker ART2 (RT6) in inbred and wild rats

2005 ◽  
Vol 57 (10) ◽  
pp. 739-749 ◽  
Author(s):  
Stefan Rothenburg ◽  
Friedrich Haag ◽  
Friedrich Koch-Nolte ◽  
Christine Carter ◽  
Margaret Graham ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Multiple Alleles ◽  
Wild Rats ◽  
Differentiation Marker

scholarly journals Characterization of subsets of CD4+ memory T cells reveals early branched pathways of T cell differentiation in humans

2005 ◽  
Vol 102 (22) ◽  
pp. 7916-7921 ◽  
Author(s):  
K. Song ◽  
R. L. Rabin ◽  
B. J. Hill ◽  
S. C. De Rosa ◽  
S. P. Perfetto ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Memory T Cells ◽  
T Cell Differentiation
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