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Protein prenylation drives discrete signaling programs for the differentiation and maintenance of effector Treg cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE158863 | GEO | 2021/01/20

REPOSITORIES: GEO

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Protein prenylation drives discrete signaling programs for the differentiation and maintenance of effector Treg cells [Pggt1b_ATACseq]

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Protein prenylation drives discrete signaling programs for the differentiation and maintenance of effector Treg cells [Fntb_ATACseq]

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Protein Prenylation Drives Discrete Signaling Programs for the Differentiation and Maintenance of Effector T<sub>reg</sub> Cells.

Project description:Effector regulatory T (eTreg) cells are essential for immune tolerance and depend upon T cell receptor (TCR) signals for generation. The immunometabolic signaling mechanisms that promote the differentiation and maintenance of eTreg cells remain unclear. Here, we show that isoprenoid-dependent posttranslational lipid modifications dictate eTreg cell accumulation and function by intersecting with TCR-induced intracellular signaling. We find that isoprenoids are essential for activated Treg cell suppressive activity, and Treg cell-specific deletion of the respective farnesylation- and geranylgeranylation-promoting enzymes Fntb or Pggt1b leads to the development of fatal autoimmunity, associated with reduced eTreg cell accumulation. Mechanistically, Fntb promotes eTreg cell maintenance by regulating mTORC1 activity and ICOS expression. In contrast, Pggt1b acts as a rheostat of TCR-dependent transcriptional programming and Rac-mediated signaling for establishment of eTreg cell differentiation and immune tolerance. Therefore, our results identify bidirectional metabolic signaling, specifically between immunoreceptor signaling and metabolism-mediated posttranslational lipid modifications, for the differentiation and maintenance of eTreg cells.

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Protein prenylation drives discrete signaling programs for the differentiation and maintenance of effector Treg cells [Microarray Dataset 3]

Project description:An interplay between immune signals, isoprenoids-mediated protein prenylation, and intracellular signaling for the differentiation and maintenance of eTreg cells. We used microarrays to compare the global transcription profiles of in vitro activated CD4+YFP+CD44loCD62Lhi cTreg cells sorted from Foxp3YFP-Cre mice and activated by 10 ug/ml anti-CD3/28 antibodies plus 200 U/ml IL-2 for different time points in the presence of prenylation inhibitors

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Protein prenylation drives discrete signaling programs for the differentiation and maintenance of effector Treg cells [Microarray Dataset 2]

Project description:An interplay between immune signals, isoprenoids-mediated protein prenylation, and intracellular signaling for the differentiation and maintenance of eTreg cells. We used microarrays to compare the global transcription profiles of CD4+YFP+Treg cells from Foxp3Cre Pggt1bfl/wt and Foxp3Cre Pggt1bfl/fl mixed bone marrow chimeras

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