Inflammation-induced Id2 promotes plasticity in regulatory T cells

Hwang, Sung Min; Sharma, Garima; Verma, Ravi; Byun, Seohyun; Rudra, Dipayan; Im, Sungbin

doi:10.1038/s41467-018-07254-2

Cited by 51 publications

(57 citation statements)

References 51 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, IL-10 production in response to allergen exposure may be stochastic and not necessarily predicated upon past production of IL-10. This model is perhaps consistent with past reports of phenotypic plasticity in induced Foxp3+ regulatory T cells (Joetham et al, 2017; Hwang et al, 2018), and between T-helper subsets in general (Zhu and Paul, 2010). Notably, the data presented here involving naturally arising Tr1-like cells stands in contrast to more phenotypically stable Tr1-like cells that have been engineered or differentiated in vitro (Gregori and Roncarolo, 2018).…”

Section: Discussionsupporting

confidence: 92%

Natural Tr1-like cells do not confer long-term tolerogenic memory

Yadava

Medina

Ishak

et al. 2019

eLife

View full text Add to dashboard Cite

IL-10-producing Tr1 cells promote tolerance but their contributions to tolerogenic memory are unclear. Using 10BiT mice that carry a Foxp3-eGFP reporter and stably express CD90.1 following IL-10 production, we characterized the spatiotemporal dynamics of Tr1 cells in a house dust mite model of allergic airway inflammation. CD90.1+Foxp3-IL-10+ Tr1 cells arise from memory cells and rejoin the tissue-resident memory T-cell pool after cessation of IL-10 production. Persistent antigenic stimulation is necessary to sustain IL-10 production and Irf1 and Batf expression distinguishes CD90.1+Foxp3-IL-10+ Tr1 cells from CD90.1+Foxp3-IL-10- ‘former’ Tr1. Depletion of Tr1-like cells after primary sensitization exacerbates allergic airway inflammation. However, neither transfer nor depletion of former Tr1 cells influences either Tr1 numbers or the inflammatory response during subsequent allergen memory re-challenge weeks later. Together these data suggest that naturally-arising Tr1 cells do not necessarily give rise to more Tr1 upon allergen re-challenge or contribute to tolerogenic memory. This phenotypic instability may limit efforts to re-establish tolerance by expanding Tr1 in vivo.

show abstract

Section: Discussionsupporting

confidence: 92%

Natural Tr1-like cells do not confer long-term tolerogenic memory

Yadava

Medina

Ishak

et al. 2019

eLife

View full text Add to dashboard Cite

show abstract

“…Taken together, our work puts forward the possibility by intervention with these molecules to reduce the plasticity of these Tregs. 32 Taken together, the findings in our paper suggest another novel mechanism by which circRNAs could regulate the impaired function of Tregs in psoriasis. This opens a new field of research for elucidation of circRNAs in the pathogenesis of dysfunctional Tregs in different autoimmune diseases.…”

Section: Discussionsupporting

confidence: 55%

“…Taken together, our work puts forward the possibility by intervention with these molecules to reduce the plasticity of these Tregs. 32 …”

Section: Discussionmentioning

confidence: 99%

hsa_circ_0003738 Inhibits the Suppressive Function of Tregs by Targeting miR-562/IL-17A and miR-490-5p/IFN-γ Signaling Pathway

Yang

Zhang

Bai

et al. 2020

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Dysfunction in the suppressive function of regulatory T cells (Tregs) has been related to the pathogenesis of psoriasis. Accumulating evidence has demonstrated the importance of circular RNAs (circRNAs) in regulating various biological process, such as cell proliferation, apoptosis, etc. However, the role of circR-NAs in modulating the suppressive functions of psoriatic Tregs and the underlying mechanisms have not been investigated. Here, by using circRNA microarray analysis, we discovered four upregulated and four downregulated circRNAs in psoriatic Tregs. Quantitative real-time PCR further confirmed a significant increase of circ_0003738 in psoriatic Tregs. Importantly, knockdown of circ_0003738 by lentivirus in psoriatic Tregs could restore their suppressive functions via inhibiting the secretion of proinflammatory cytokines interleukin-17A (IL-17A) and interferon (IFN)-g. Moreover, we found that circ_0003738 could bind to miR-562 to release the inhibition of target gene IL-17RA (IL-17 receptor A), thus promoting IL-17A signaling in psoriatic Tregs. In parallel, circ_0003738 acted also as a sponge for miR-490-5p and relieved inhibition for the target gene IFNGR2, which promoted IFN-g signaling in psoriatic Tregs. Our study demonstrated that upregulated circ_0003738 decreased the suppressive function of psoriatic Tregs via the miR-562/IL17RA and miR-490-5p/IFNGR2 (IFN-g receptor 2) axis, which indicated the involvement of circRNAs in the pathogenesis of dysfunctional Tregs. These findings will provide new therapeutic targets for the treatment of psoriasis.

show abstract

“…TCR signaling decreases expression of Id3 and increases expression of Id2 in Treg cells in vitro. A tight regulation of Id protein expression is likely important for Treg cells, as Id2 overexpression impairs stability and the immune suppressive functions of Treg cells [64]. In contrast, a recent study has revealed that E-proteins suppress differentiation of eTreg cells, as E2A/HEB double knockout Treg cells exhibit increased expression of effector Treg signature molecules, such as IRF4, ICOS, CD103, RORγt, and KLRG1, and enhanced eTreg stability and suppressive function.…”

Section: Transcription Factors In a Core Etreg Transcriptional Promentioning

confidence: 99%

Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells

Koizumi

Ishikawa

2019

Cells

View full text Add to dashboard Cite

Foxp3-expressing regulatory T (Treg) cells can suppress the activity of various types of immune cells and play key roles in the maintenance of self-tolerance and in the regulation of immune responses against pathogens and tumor cells. Treg cells consist of heterogeneous subsets that have distinct phenotypes and functions. Upon antigen stimulation, naïve-like thymus-derived Treg cells, which circulate in secondary lymphoid organs, can differentiate into effector Treg (eTreg) cells and migrate to and control immune homeostasis of peripheral tissues. eTreg cells are heterogeneous in terms of their ability to localize to specific tissues and suppress particular types of immune responses. Differentiation and function of diverse eTreg subsets are regulated by a variety of transcription factors that are activated by antigens and cytokines. In this article, we review the current understanding of the transcriptional regulation of differentiation and function of eTreg cells.

show abstract

Inflammation-induced Id2 promotes plasticity in regulatory T cells

Cited by 51 publications

References 51 publications

Natural Tr1-like cells do not confer long-term tolerogenic memory

Natural Tr1-like cells do not confer long-term tolerogenic memory

hsa_circ_0003738 Inhibits the Suppressive Function of Tregs by Targeting miR-562/IL-17A and miR-490-5p/IFN-γ Signaling Pathway

Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells

Contact Info

Product

Resources

About