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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [single cell RNA-seq]

ABSTRACT: T regulatory (Treg) cells play an essential role in suppressing the response of immune effector cells. The zinc finger protein 36 (ZFP36) family of RNA binding proteins (RBP) have been demonstrated to have crucial roles in development, stress responses and inflammation. Treg-restricted deletion of ZFP36L1 leads to a loss of immune homeostasis with an expansion of effector cell subsets and over-production of inflammatory cytokines, with the phenotype exacerbated with the combined deletion of ZFP36L2. Single cell RNA seq analyses revealed a Treg transcriptional profile that was biased towards an activated phenotype. We report that ZFP36L1 and ZFP36L2 play a key role in regulating Treg sensitivity to cytokine signalling. By limiting the IFNg signalling pathway these RBP influence Th-type cell transcriptional programs and promote Treg responsiveness to IL-2 and IL-7. Together our results reveal cell intrinsic effects of these RBP important for Treg function.

ORGANISM(S): Mus musculus

PROVIDER: GSE240517 | GEO | 2024/08/08

REPOSITORIES: GEO

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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [bulk RNA-seq]

Project description:T regulatory (Treg) cells play an essential role in suppressing the response of immune effector cells. The zinc finger protein 36 (ZFP36) family of RNA binding proteins (RBP) have been demonstrated to have crucial roles in development, stress responses and inflammation. Treg-restricted deletion of ZFP36L1 leads to a loss of immune homeostasis with an expansion of effector cell subsets and over-production of inflammatory cytokines, with the phenotype exacerbated with the combined deletion of ZFP36L2. Single cell RNA seq analyses revealed a Treg transcriptional profile that was biased towards an activated phenotype. We report that ZFP36L1 and ZFP36L2 play a key role in regulating Treg sensitivity to cytokine signalling. By limiting the IFNg signalling pathway these RBP influence Th-type cell transcriptional programs and promote Treg responsiveness to IL-2 and IL-7. Together our results reveal cell intrinsic effects of these RBP important for Treg function.

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