Maintenance of CCL5 mRNA stores by post‐effector and memory CD8 T cells is dependent on transcription and is coupled to increased mRNA stability

Marçais, Antoine; Tomkowiak, Martine; Walzer, Thierry; Coupet, Charles-Antoine; Ravel‐Chapuis, Aymeric; Marvel, Jacqueline

doi:10.1002/eji.200636259

Cited by 22 publications

(16 citation statements)

References 36 publications

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“…The stabilization of the mRNAs encoding important inflammatory mediators2057 constitutes an important paradigm of HuR's functions. Many inflammatory mediator mRNAs known to be regulated at the stability level58596061, and shown subjected to PARP1 regulation in the present study, are ARE-containing, such as Il1β , Cxcl1 , Cxcl2 and Ccl11 . Moreover, although there is no study addressing its stability, Il11 mRNA contains typical AREs in its 3′-UTR, and PARP1 inhibition resulted in a significant decrease in its mRNA stability as shown by plate-based real-time PCR arrays.…”

Section: Discussionsupporting

confidence: 49%

PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR

Han

Guo

et al. 2017

Nat Commun

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Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding. Increases in mRNA level or stability of pro-inflammatory cytokines/chemokines are abolished by PARP1 ablation or inhibition, or blocked in D226A HuR-expressing cells. The present study demonstrates a mechanism to regulate gene expression at the post-transcriptional level, and suggests that blocking the interaction of PARP1 with HuR could be a strategy to treat inflammation-related diseases that involve increased mRNA stability.

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Section: Discussionsupporting

confidence: 49%

PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR

Han

Guo

et al. 2017

Nat Commun

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“…We have previously shown that in memory CD8 T cells Ccl5 expression is downregulated by IL-4 in a STAT6-dependent manner (6). Thus, we investigated whether STAT6 was also involved in the regulation of Nkg2d expression by IL-4 in T IM .…”

Section: Il-4 Regulates Nkg2d Expression In Memory Cd8 T Cells Via a mentioning

confidence: 93%

“…These elevated CCL5 mRNA levels have been observed in memory CD8 T cells generated in a variety of systems (4,5). They are maintained through constitutive transcription of the Ccl5 gene and increased stabilization of the mRNA (6). The increased efficiency of memory CD8 responses also arise from their lower activation threshold compared with naive cells.…”

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confidence: 91%

Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells

Ventre

Brinza

Schicklin

et al. 2012

The Journal of Immunology

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IL-4 is one of the main cytokines produced during Th2-inducing pathologies. This cytokine has been shown to affect a number of immune processes such as Th differentiation and innate immune responses. However, the impact of IL-4 on CD8 T cell responses remains unclear. In this study, we analyzed the effects of IL-4 on global gene expression profiles of Ag-induced memory CD8 T cells in the mouse. Gene ontology analysis of this signature revealed that IL-4 regulated most importantly genes associated with immune responses. Moreover, this IL-4 signature overlapped with the set of genes preferentially expressed by memory CD8 T cells over naive CD8 T cells. In particular, IL-4 downregulated in vitro and in vivo in a STAT6-dependent manner the memory-specific expression of NKG2D, thereby increasing the activation threshold of memory CD8 T cells. Furthermore, IL-4 impaired activation of memory cells as well as their differentiation into effector cells. This phenomenon could have an important clinical relevance as patients affected by Th2 pathologies such as parasitic infections or atopic dermatitis often suffer from viral-induced complications possibly linked to inefficient CD8 T cell responses.

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“…In addition, they contain 600 times more CCL5 mRNAs than naive F5 CD8 T cells (Fig. 2E), indicating that they have acquired the capacity to store CCL5 messengers, another functional feature of memory CD8 T cells (21)(22)(23)(24). Moreover, they express increased levels of T-bet and eomesodermin (Fig.…”

Section: F5 Cd44/122 Int Memory Cd8 T Cells Are Generated Under Sterimentioning

confidence: 93%

Characterization of a CD44/CD122int Memory CD8 T Cell Subset Generated under Sterile Inflammatory Conditions

Mbitikon-Kobo

Vocanson

Michallet

et al. 2009

The Journal of Immunology

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Most memory CD8 T cell subsets that have been hitherto defined are generated in response to infectious pathogens. In this study, we have characterized the CD8 T cells that survive priming conditions, devoid of pathogen-derived danger signals. In both a TCR-transgenic model and a model of contact hypersensitivity, we show that the priming of naive CD8 T cells under sterile inflammatory conditions generates memory. The corresponding memory CD8 T cells can be identified by their intermediate expression levels of CD44 and CD122. We also show that CD44/122 int memory CD8 T cells spontaneously develop in wild type mice and that they display intermediate levels of several other memory traits including functional (IFN-␥ secretion capacity, CCL5 messenger stores), phenotypic, and molecular (T-bet and eomesodermin expression levels) features. We finally show that they correspond to an early differentiation stage and can further differentiate in CD44/122 high memory T cells. Altogether, our results identify a new memory CD8 T cell subset that is generated under sterile inflammatory conditions and involved in the recall contact hypersensitivity reactions that are responsible for allergic contact dermatitis.

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Maintenance of CCL5 mRNA stores by post‐effector and memory CD8 T cells is dependent on transcription and is coupled to increased mRNA stability

Cited by 22 publications

References 36 publications

PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR

PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR

Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells

Characterization of a CD44/CD122int Memory CD8 T Cell Subset Generated under Sterile Inflammatory Conditions

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