Differential Roles of IL-2 Signaling in Developing versus Mature Tregs

Fan, Martin; Low, Jun Siong; Tanimine, Naoki; Finn, Kelsey; Priyadharshini, Bhavana; Germana, Sharon; Kaech, Susan M.; Turka, Laurence A.

doi:10.1016/j.celrep.2018.10.002

Cited by 118 publications

(98 citation statements)

References 50 publications

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“…The importance of CD25 - Tregs is unclear: they exhibit a highly activated phenotype characterized by elevated ICOS and PD-1 expression, suggestive of chronic antigen exposure, but the majority have not been attributed any specific function – aside from the notable subpopulation that exist as Tfr cells. We confirmed that the loss of CD25 - Tregs following JunB deletion does not result from loss of Foxp3 expression, which is aligned with a recent report showing that CD25 - Tregs are not particularly unstable 34 . Using RNA-seq, we found that JunB-deficiency in CD25 - PP Tregs leads to reduced expression of genes involved in several metabolic pathways – notably fatty acid metabolism and oxidative phosphorylation.…”

Section: Discussionsupporting

confidence: 91%

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JunB controls intestinal effector programs in regulatory T cells

Wheaton

Ciofani

2019

Preprint

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Foxp3-expressing regulatory T (Treg) cells are critical mediators of immunological tolerance to both self and microbial antigens. Tregs activate context-dependent transcriptional programs to adapt effector function to specific tissues; however, the factors controlling tissue-specific gene expression in Tregs remain unclear. Here, we find that the AP-1 transcription factor JunB enables the environmental adaptation of Tregs by facilitating tissue-specific transcriptional programming. Treg-specific ablation of JunB results in immune dysregulation characterized by enhanced colonic T cell accumulation and cytokine production; however – in contrast to its classical binding-partner BATF – JunB is dispensable for both effector Tregs and the majority of Treg subsets. Rather, JunB activates a transcriptional program facilitating the maintenance of CD25- Tregs – including follicular Tregs – and a separate effector program in colonic Tregs that includes the cytolytic molecules Granzymes A and B. Therefore, JunB is a novel and essential regulator of tissue-specific Treg effector programming.

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Section: Discussionsupporting

confidence: 91%

“…Next, we sought to explain the unique dependence of CD25 - Tregs on JunB. Consistent with previous reports 32, 34 , we noted that CD25 - Tregs displayed reduced expression of Foxp3, the lineage-defining TF for Tregs (Fig. 3H).…”

Section: Resultssupporting

confidence: 81%

JunB controls intestinal effector programs in regulatory T cells

Wheaton

Ciofani

2019

Preprint

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“…The purpose of systems biology is to combine comprehensive biological data from varied experimental approaches to realize complex interactions at the molecular stage [11]. One of the important protein components of the human immune system is CD25 expressed on cell surface of Treg cells [1].…”

Section: Discussionmentioning

confidence: 99%

“…These CD4+ Foxp3+ Tregs express high levels of CD25 (known as IL-2RA). Tregs are the solitary immune cell type identi ed to express the full heterotrimeric receptor including CD25, CD122 (IL-2RB), and CD132 (IL-2RG), constitutively [1]. The IL-2 functions via high and low a nity in these cell surface receptors.…”

Section: Introductionmentioning

confidence: 99%

Systems Biology Unraveled the Relationship of lncRNA OIP5-AS1 with CD25 and its Co-Expression Analysis in Cancers

Dehbashi

Hojati

Motovali-Bashi

et al. 2020

Preprint

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Background: Treg cells function in the immune homeostasis, these cells express high level of CD25. Even though the molecular mechanisms of CD25-mediated signaling pathways has been reported, some questions are still unclear, e.g. the relationship and function of the relative lncRNA. It is known that the CD25 expression levels are various among different cancers. Thus, we intended to dissect systems biology of a lncRNA pertained to CD25 and CD25 protein interactors-targeting miRNAs. Methods: Apart from using the available RNA-seq data, the co-expression analysis of the lncRNA pertained to some cancers was performed. Our analysis was done for protein interactors of CD25 by STRING 11.0, ShinyGO v0.60 and KEGG web servers were used for enrichment and network analysis of CD25. TargetScan 7.2, miRTargetLink Human and mirDIP were applied for determining the CD25 and CD25 interactors-targeting miRNAs. To find the lncRNA-miRNA and lncRNA-protein interactions, starBase v3.0, LncBase Predicted v.2 and SFPEL-LPI were recruited, respectively. Also, using Co-LncRNA, the co-expressed lncRNA analysis and the relative signaling pathways in some cancers including bladder, breast, head and neck, kidney, liver, lung, prostate and thyroid cancers using RNA-seq data were achieved. Results: OIP5-AS1 was shown to have the interaction with CD25 and CD25 protein interactors-targeting miRNAs. In addition, the co-expression of OIP5-AS1 in cancers and their signaling pathways was identified. Conclusions: Possibly, OIP5-AS1 can effect on CD25 expression in all relative signaling pathways of these cancers.

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“…Treg cells are mainly dependent upon IL‐2 signalling for both their thymic and peripheral differentiation and for their survival, although IL‐15 and IL‐7 can partially substitute for IL‐2 in maintaining Treg cell survival in the genetic absence of IL‐2or following Treg‐specific disruption of CD25 expression, respectively. This leads to the question of whether IL‐2 production within tumours is required for maintenance of intratumoural Treg cell populations and what the dominant cellular source of IL‐2 is within tumours (reviewed in ref.…”

Section: Regulation Of Treg Cells In Cancermentioning

confidence: 99%

Regulation of regulatory T cells in cancer

2019

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Summary The inflammatory response to transformed cells forms the cornerstone of natural or therapeutically induced protective immunity to cancer. Regulatory T (Treg) cells are known for their critical role in suppressing inflammation, and therefore can antagonize effective anti‐cancer immune responses. As such, Treg cells can play detrimental roles in tumour progression and in the response to both conventional and immune‐based cancer therapies. Recent advances in our understanding of Treg cells reveal complex niche‐specific regulatory programmes and functions, which are likely to extrapolate to cancer. The regulation of Treg cells is reliant on upstream cues from haematopoietic and non‐immune cells, which dictates their genetic, epigenetic and downstream functional programmes. In this review we will discuss how Treg cells are themselves regulated in normal and transformed tissues, and the implications of this cross talk on tumour growth.

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Differential Roles of IL-2 Signaling in Developing versus Mature Tregs

Cited by 118 publications

References 50 publications

JunB controls intestinal effector programs in regulatory T cells

JunB controls intestinal effector programs in regulatory T cells

Systems Biology Unraveled the Relationship of lncRNA OIP5-AS1 with CD25 and its Co-Expression Analysis in Cancers

Regulation of regulatory T cells in cancer

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