ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis [bulk RNA-seq - creERT2]
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ABSTRACT:
PROVIDER: PRJNA1208583 | ENA |
REPOSITORIES: ENA
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Project description:RNA binding proteins (RBP) of the ZFP36 family limit the differentiation and effector functions of CD4 and CD8 T cells, but little is known of their expression or function in regulatory T cells (Treg). By Treg-restricted deletion of Zfp36 family members we identify the essential role of Zfp36l1 and Zfp36l2 in Treg to maintain immune homeostasis. Mice with Tregs deficient in these RBP display an inflammatory phenotype with an expansion in the numbers of type-2 conventional dendritic cells, T effector cells, T follicular helper and germinal center B cells and elevated serum cytokines and immunoglobulins. In the absence of Zfp36l1 and Zfp36l2, the pool of cycling CTLA-4 in naïve Treg was reduced, Tregs were less sensitive to IL-2 and IL-7 but were more sensitive to IFNγ. In mice lacking both RBP in Treg, the deletion of a single allele of Ifng is sufficient to ameliorate the pathology. Thus, ZFP36L1 and ZFP36L2 regulate multiple pathways that enable Tregs to enforce immune homeostasis.
2025-01-13 | GSE286303 | GEO
Project description:ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis
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Project description:ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis [bulk RNA-seq]
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Project description:ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis [single cell RNA-seq]
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Project description:RNA binding proteins (RBP) of the ZFP36 family limit the differentiation and effector functions of CD4 and CD8 T cells, but little is known of their expression or function in regulatory T cells (Treg). By Treg-restricted deletion of Zfp36 family members we identify the essential role of Zfp36l1 and Zfp36l2 in Treg to maintain immune homeostasis. Mice with Tregs deficient in these RBP display an inflammatory phenotype with an expansion in the numbers of type-2 conventional dendritic cells, T effector cells, T follicular helper and germinal center B cells and elevated serum cytokines and immunoglobulins. In the absence of Zfp36l1 and Zfp36l2, the pool of cycling CTLA-4 in naïve Treg was reduced, Tregs were less sensitive to IL-2 and IL-7 but were more sensitive to IFNγ. In mice lacking both RBP in Treg, the deletion of a single allele of Ifng is sufficient to ameliorate the pathology. Thus, ZFP36L1 and ZFP36L2 regulate multiple pathways that enable Tregs to enforce immune homeostasis.
2024-08-08 | GSE244619 | GEO
Project description:RNA binding proteins (RBP) of the ZFP36 family limit the differentiation and effector functions of CD4 and CD8 T cells, but little is known of their expression or function in regulatory T cells (Treg). By Treg-restricted deletion of Zfp36 family members we identify the essential role of Zfp36l1 and Zfp36l2 in Treg to maintain immune homeostasis. Mice with Tregs deficient in these RBP display an inflammatory phenotype with an expansion in the numbers of type-2 conventional dendritic cells, T effector cells, T follicular helper and germinal center B cells and elevated serum cytokines and immunoglobulins. In the absence of Zfp36l1 and Zfp36l2, the pool of cycling CTLA-4 in naïve Treg was reduced, Tregs were less sensitive to IL-2 and IL-7 but were more sensitive to IFNγ. In mice lacking both RBP in Treg, the deletion of a single allele of Ifng is sufficient to ameliorate the pathology. Thus, ZFP36L1 and ZFP36L2 regulate multiple pathways that enable Tregs to enforce immune homeostasis.
2024-08-08 | GSE240517 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-08 | GSE244621 | GEO
Project description:Tristetraprolin/ZFP36/TTP and ELAVL1/HuR are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embyonic kidney cells and examined combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Among the targets ZFP36 binds and negatively regulates the mRNA of genes encoding proteins necessary for immune function and cancer, and other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance from ZFP36 overexpression independent of effects from confounding features, such as 3M-bM-^@M-^Y UTR length. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes. ZFP36 preferentially interacts with and regulates AU-rich sequences while ELAVL1 prefers predominantly U- and CU-rich sequences. RNA target specificity identified by global in vivo ZFP36-mRNA interactions were quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 both bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to untangle the in vivo combinatorial regulation by RNA-binding proteins. Five biological replicates for each of the four sample classes -> Parental and EGFP-ZFP36 HEK293 cells treated with either doxycycline or water.
2013-12-24 | E-GEOD-53183 | biostudies-arrayexpress
Project description:Tristetraprolin/ZFP36/TTP and ELAVL1/HuR are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embyonic kidney cells and examined combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Among the targets ZFP36 binds and negatively regulates the mRNA of genes encoding proteins necessary for immune function and cancer, and other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance from ZFP36 overexpression independent of effects from confounding features, such as 3M-bM-^@M-^Y UTR length. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes. ZFP36 preferentially interacts with and regulates AU-rich sequences while ELAVL1 prefers predominantly U- and CU-rich sequences. RNA target specificity identified by global in vivo ZFP36-mRNA interactions were quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 both bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to untangle the in vivo combinatorial regulation by RNA-binding proteins. FLAG-HA ZFP36
2013-12-24 | E-GEOD-53184 | biostudies-arrayexpress
Project description:Tristetraprolin/ZFP36/TTP and ELAVL1/HuR are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embyonic kidney cells and examined combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Among the targets ZFP36 binds and negatively regulates the mRNA of genes encoding proteins necessary for immune function and cancer, and other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance from ZFP36 overexpression independent of effects from confounding features, such as 3’ UTR length. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes. ZFP36 preferentially interacts with and regulates AU-rich sequences while ELAVL1 prefers predominantly U- and CU-rich sequences. RNA target specificity identified by global in vivo ZFP36-mRNA interactions were quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 both bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to untangle the in vivo combinatorial regulation by RNA-binding proteins.
2013-12-24 | GSE53183 | GEO