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

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

ORGANISM(S): Mus musculus

PROVIDER: GSE244621 | 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.

2024-08-08 | GSE244619 | GEO

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

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

Project description:An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis

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

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

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

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

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ZFP36 RNA binding proteins restrain T-cell activation kinetics and anti-viral immunity

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-03-01 | GSE96076 | GEO

ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity.

Project description:Dynamic post-transcriptional control of RNA expression by RNA-binding proteins (RBPs) is critical during immune response. ZFP36 RBPs are prominent inflammatory regulators linked to autoimmunity and cancer, but functions in adaptive immunity are less clear. We used HITS-CLIP to define ZFP36 targets in mouse T cells, revealing unanticipated actions in regulating T-cell activation, proliferation, and effector functions. Transcriptome and ribosome profiling showed that ZFP36 represses mRNA target abundance and translation, notably through novel AU-rich sites in coding sequence. Functional studies revealed that ZFP36 regulates early T-cell activation kinetics cell autonomously, by attenuating activation marker expression, limiting T cell expansion, and promoting apoptosis. Strikingly, loss of ZFP36 in vivo accelerated T cell responses to acute viral infection and enhanced anti-viral immunity. These findings uncover a critical role for ZFP36 RBPs in restraining T cell expansion and effector functions, and suggest ZFP36 inhibition as a strategy to enhance immune-based therapies.

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The ZFP36 family of RNA-binding proteins regulates homeostatic and autoreactive T cell responses

Project description:This SuperSeries is composed of the SubSeries listed below.

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Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis.

Project description:This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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