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

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

ORGANISM(S): Mus musculus

PROVIDER: GSE192956 | GEO | 2022/08/08

REPOSITORIES: GEO

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

Project description:RNA binding proteins are important regulators of T cell activation, proliferation, and cytokine production. The zinc finger protein 36 (ZFP36) family genes (Zfp36, Zfp36l1, and Zfp36l2) encode RNA binding proteins that promote the degradation of transcripts containing AU-rich elements. Numerous studies have demonstrated both individual and shared functions of the ZFP36 family in immune cells, but their collective function in T cells remains unclear. Here, we found a redundant and critical role for the ZFP36 proteins in regulating T cell quiescence. T cell-specific deletion of all three ZFP36 family members in mice resulted in early lethality, immune cell activation, and multiorgan pathology characterized by inflammation of the eyes, central nervous system, kidneys, and liver. Mice with T cell-specific deletion of any two Zfp36 genes were protected from this spontaneous syndrome. Triply deficient T cells overproduced proinflammatory cytokines, including IFN-γ, TNF, and GM-CSF, due to increased mRNA stability of these transcripts. Unexpectedly, T cell-specific deletion of both Zfp36l1 and Zfp36l2 rendered mice resistant to experimental autoimmune encephalomyelitits due to failed priming of antigen-specific CD4+ T cells. ZFP36L1 and ZFP36L2 double-deficient CD4+ T cells had poor proliferation during in vitro T helper cell polarization. Thus, the ZFP36 family redundantly regulates T cell quiescence at homeostasis, but ZFP36L1 and ZFP36L2 are specifically required for antigen-specific T cell clonal expansion.

| S-EPMC9832469 | biostudies-literature

The ZFP36 family of RNA-binding proteins regulates homeostatic and autoreactive T cell responses [mRNA-decaySeq]

Project description:These are CD44hi CD4 T splenic T cells from the indicated mice activated in vitro with anti-CD3/anti-CD28 for 24 hours. Following activation, cells were treated with Actinomycin D for the indicated time course.

2022-08-09 | GSE192954 | GEO

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

Project description:These are spleen and kidney T cells directly analyzed from the indicated mice by RNA-seq.

2022-08-09 | GSE192953 | GEO

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

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

| PRJNA793879 | ENA

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

Project description:The ZFP36 family of RNA-binding proteins regulates homeostatic and autoreactive T cell responses [RNA-Seq]

| PRJNA793882 | ENA

The ZFP36 family of RNA-binding proteins regulates homeostatic and autoreactive T cell responses [mRNA-decaySeq]

Project description:The ZFP36 family of RNA-binding proteins regulates homeostatic and autoreactive T cell responses [mRNA-decaySeq]

| PRJNA793883 | ENA

ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis

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

2024-08-08 | GSE244621 | GEO

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

Global Target mRNA Specification and Regulation by RNA-Binding Protein ZFP36/Tristetraprolin/TTP

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

2013-12-24 | E-GEOD-53185 | biostudies-arrayexpress

ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis [bulk RNA-seq]

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

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