Involvement of lncRNA IL21-AS1 in interleukin-2 and T follicular regulatory cell activation in systemic lupus erythematosus

He, Hao; Nakayamada, Shingo; Ohkubo, Naoaki; Yamagata, Kazuya; Zhang, Mingzeng; Shan, Yu; Iwata, S.; Zhang, Tong; Tanaka, Yoshiya

doi:10.1186/s13075-021-02682-w

Cited by 17 publications

(10 citation statements)

References 49 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In subsequent studies, researchers have found that IL‐2 plays a pivotal role in maintaining the suppression function of Tfrs. 245 , 246 , 247 When serum IL‐2 levels were reduced in patients with SLE, the proportion of CD4 + CXCR5 + FOXP3 – PD‐1 high Tfhs was increased, whereas the proportion of CD4 + CXCR5 + CD45RA – FOXP3 high Tfrs was decreased. 245 However, stimulation with an exogenous low dose of IL‐2 could restore the function of Tfrs and converse Tfhs to Tfrs by regulation of FOXP3 and BCL6 through histone modification.…”

Section: Treg Subsets In Autoimmune Diseasementioning

confidence: 99%

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Jiang

Zhu

Wang

et al. 2022

MedComm

View full text Add to dashboard Cite

CD4 + CD25 + regulatory T cells (Tregs), a subpopulation of naturally CD4 + T cells that characteristically express transcription factor Forkhead box P3 (FOXP3), play a pivotal role in the maintenance of immune homeostasis and the prevention of autoimmunity. With the development of biological technology, the understanding of plasticity and stability of Tregs has been further developed. Recent studies have suggested that human Tregs are functionally and phenotypically diverse. The functions and mechanisms of different phenotypes of Tregs in different disease settings, such as tumor microenvironment, autoimmune diseases, and transplantation, have gradually become hot spots of immunology research that arouse extensive attention. Among the complex functions, CD4 + CD25 + FOXP3 + Tregs possess a potent immunosuppressive capacity and can produce various cytokines, such as IL‐2, IL‐10, and TGF‐β, to regulate immune homeostasis. They can alleviate the progression of diseases by resisting inflammatory immune responses, whereas promoting the poor prognosis of diseases by helping cells evade immune surveillance or suppressing effector T cells activity. Therefore, methods for targeting Tregs to regulate their functions in the immune microenvironment, such as depleting them to strengthen tumor immunity or expanding them to treat immunological diseases, need to be developed. Here, we discuss that different subpopulations of Tregs are essential for the development of immunotherapeutic strategies involving Tregs in human diseases.

show abstract

Section: Treg Subsets In Autoimmune Diseasementioning

confidence: 99%

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Jiang

Zhu

Wang

et al. 2022

MedComm

View full text Add to dashboard Cite

show abstract

“…SNP-PCR was performed according to the instructions supplied by the manufacturer to determine the genotypes of rs1893592-A/C, as described previously [ 16 ]. On a Step One Plus system (Applied Biosystems), PCR was performed in 10 μL of reaction volume containing 1 μL of genomic DNA (20 ng/μL) from 14 RA patients (male to female 4:10), 5 μL of TaqMan Universal PCR Master Mix, 0.25 μL of VIC/FAM-labeled probe (200 nM), and 3.75 μL of double-distilled water.…”

Section: Methodsmentioning

confidence: 99%

IL-6 production through repression of UBASH3A gene via epigenetic dysregulation of super-enhancer in CD4+ T cells in rheumatoid arthritis

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Rheumatoid arthritis (RA) is associated with immune dysfunction. UBASH3A as a negative regulator of T cell receptors (TCRs) signaling is a susceptible factor in RA. The aim of this study was to determine the role of UBASH3A in RA pathogenesis, by assessing the role of super-enhancer (SE) in the control of UBASH3A expression in CD4+ T cells and the contribution of the latter in proinflammatory cytokine production in patients with RA. Methods UBASH3A mRNA and protein levels were quantified by PCR and western blotting, respectively. The cells were treated with a locked nucleic acid to inhibit enhancer RNA (eRNA) expression. Chromatin immunoprecipitation was used to identify the factors recruited to UBASH3A loci displaying SE architecture. CD4+ T cells were transfected with UBASH3A plasmids, and cytokine levels were measured by a cytometric bead array. Results UBASH3A was extracted as a RA susceptibility gene associated with SNPs in the SEs that are highly expressed in CD4+ T cells by in silico screening. UBASH3A mRNA and protein expression levels were lower in CD4+ T cells of RA patients than in the control. eRNA_1 and eRNA_3 knockdown reduced UBASH3A mRNA levels. RA patients exhibited accumulation of BTB and CNC homology 2 (BACH2), the silencing transcription factor, at the UBASH3A loci in CD4+ T cells, but not the SE-defining factor, mediator complex subunit 1 (MED1)/bromodomain 4 (BRD4). However, opposite changes were observed in the control. Stimulation of TCRs expressed on CD4+ T cells of RA patients resulted in interleukin (IL)-6 production, while UBASH3A over-expression significantly inhibited the production. Conclusions In RA, transcription of UBASH3A is suppressed via epigenetic regulation of SE in CD4+ T cells. Low UBASH3A levels result in excessive TCR signal activation with subsequent enhancement of IL-6 production.

show abstract

“…Recently, a study revealed the possible involvement of Interleukin-21 antisense RNA 1 (IL21-AS1) in the dysregulated IL-2-Tfr cell axis in patients with SLE. 84 IL21-AS1 was identified its expression reduced in both PBMCs and CD4 + T cells of SLE. Besides, the expression of IL21-AS1 in PBMCs of SLE patients is positively correlated with the expression of IL-2.…”

Section: Il21-as1mentioning

confidence: 95%

Long non‐coding RNAs in systemic lupus erythematosus: New insights into disease pathogenesis and diagnosis

Chen

Cheng

et al. 2022

Scand J Immunol

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a remarkable heterogeneous autoimmune disease that is sometimes hard to diagnose at the early stage and can lead to premature mortality. Long non‐coding RNAs (lncRNAs) are a class of non‐protein‐coding RNAs greater than 200 nucleotides in length that can regulate gene expression in various human diseases, including SLE. Peripheral blood samples and renal tissue samples from SLE patients were used for study. Abnormally expressed lncRNAs in SLE have been shown to influence several signalling pathways, including the IFN‐I, MAPK and WNT pathways. This can affect cellular phenotypes like cell activation, differentiation skewing, cytokine production and cell apoptosis. Many of the reported lncRNAs may be useful for diagnosing, evaluating progression and predicting potential organ damage in SLE patients. While numerous lncRNAs play important roles in SLE, more basic and clinical studies are warranted to clarify the function of these regulatory molecules and determine their diagnostic value.

show abstract

Involvement of lncRNA IL21-AS1 in interleukin-2 and T follicular regulatory cell activation in systemic lupus erythematosus

Cited by 17 publications

References 49 publications

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

IL-6 production through repression of UBASH3A gene via epigenetic dysregulation of super-enhancer in CD4+ T cells in rheumatoid arthritis

Long non‐coding RNAs in systemic lupus erythematosus: New insights into disease pathogenesis and diagnosis

Contact Info

Product

Resources

About