Low-dose IL-2 mitigates glucocorticoid-induced Treg impairment and promotes improvement of SLE

Zhou, Haotian; Zhao, Xiaozhen; Zhang, Ruijun; Miao, Miao; Pei, Wenwen; Li, Yimin; He, Jing; Li, Zhanguo; Sun, Xiaolin

doi:10.1038/s41392-023-01350-6

Cited by 7 publications

(5 citation statements)

References 8 publications

(9 reference statements)

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“…B10 is a functionally defined regulatory B-cell subset that plays vital role in the control of inflammation and autoimmune diseases, although it is present at low numbers in peripheral blood [ 27 ]. Specifically, it has been reported that B10 may ameliorate the progression of SLE, similar to Treg [ 16 , 28 ]. In addition, it has been shown that ILC2, which is characterized by the release of type 2 cytokines including IL-5, IL-9, and IL-13, etc., regulates a number of immune responses and functions protectively in autoimmunity by inhibiting the synthesis of IL-27 and by generating IL-9 to interact with regulatory T cells [ 18 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Elevation of Metrnβ and Its Association with Disease Activity in Systemic Lupus Erythematosus

Zhang,

Cai,

et al. 2023

IJMS

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Systemic lupus erythematosus (SLE) is an auto-immune disease, the pathogenesis of which remains to be fully addressed. Metrnβ is a novel cytokine involved in the pathogenesis of inflammatory disease, but its regulatory roles in SLE are unclear. We aimed to comprehensively investigate the clinical value of Metrnβ in SLE. A massive elevation of circulating Metrnβ levels was observed in SLE, and patients with an active phase displayed higher Metrnβ concentrations than those with inactive phases. Additionally, we found that Metrnβ expression was positively correlated with clinical indicators of SLE. Longitudinal cytokine and chemokine profiles revealed a disturbed immune response in SLE, with high activity profiles displayed severe pathogenic inflammation, and a positive correlation of the serum Metrnβ with CXCL9, IL10, IL18 and IL1RA was observed as well. Moreover, Metrnβ expressions exhibited an inverse correlation with Treg and B10. Of note, a significant decrease of ILC2 was found in SLE, and there was a negative correlation of Metrnβ with ILC2 as well. Further ROC analysis showed that the area under the curve (AUC) for Metrnβ was 0.8250 (95% CI: 0.7379–0.9121), with a cutoff value of 1131 pg/mL to effectively distinguish SLE patients from healthy controls. Our study herein demonstrated for the first time that Metrnβ values were increased and were immunologically correlated with SLE activity, which could be utilized as an alternative biomarker for the early identification and predicting of the immuno-response of SLE.

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Section: Discussionmentioning

confidence: 99%

Elevation of Metrnβ and Its Association with Disease Activity in Systemic Lupus Erythematosus

Zhang,

Cai,

et al. 2023

IJMS

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“…Only then can we ensure that the most appropriate treatment regimen is tailored for each patient to maximize their survival and quality of life. We expect more breakthroughs and more victories in the protracted battle against tiny tumors [7][8][9][10][11][12]. ISSN 2706-6819 Vol.6, Issue 3: 28-32, DOI: 10.25236/IJFM.2024.060305…”

Section: The Role Of Serum Il-10 In Treating the Mechanisms Of Immune...mentioning

confidence: 99%

Analysis of the role of serum IL-2R, IL-6, IL-8, IL-10, and TNF-α in the treatment of immune escape mechanisms in patients with minimal ma tumors

2024

IJFM

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Tumor immune escape refers to the phenomenon that tumor cells evade the recognition and attack of the body's immune system through a series of mechanisms, thus surviving and multiplying in the body. These mechanisms include, but are not limited to, low immunity, recognition as autologous antigen, antigenic modulation, tumor-induced immunosuppressive effects, and areas of tumor-induced generation immunity. Tumor cells often have low immunogenicity, i. e. they lack sufficient epitopes to stimulate the body's immune system. In addition, tumor cells can also produce immune suppressive molecules or cells by interacting with host cells, thus inhibiting the body's immune response. In addition, tumor cells can also produce immune suppressive molecules or cells by interacting with host cells, thus inhibiting the body's immune response. In this paper, the role of serum IL-2R, IL-6, IL-8, IL-10 and 1 TNF-α in the treatment of immune escape mechanism in patients was analyzed for reference.

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“…Numerous studies have recently discussed IL-2 in treating SLE patients ( Table 2 ). A total of eight studies evaluated the effect of low-dose human IL-2 in treatment of SLE patients from north Chinese SLE patients (randomized controlled trials, RCTs) ( 42 , 43 , 149 – 154 ). SLE patients received three cycles of human IL-2 treatment (1 million IU every other day for 2 weeks, followed by a 2-week break), showing reduced SLEDAI score, less myositis, fever, alopecia, vasculitis, arthritis, oral ulcer, low rate of infection, decreased number of CXCR5 + PD-1 + CCR7 lo Tfh cells, CCR6 + CXCR3 − CCR4 + CCR7 lo Th17 cells, and CD4 − CD8 − αβ T cells at the 12th week, and an elevated proportion of CXCR5 + PD-1 lo Treg cells and CXCR5 + PD-1 hi Treg cells and ratios of CXCR5 + PD-1 lo Treg/Tfh, CXCR5 + PD-1 hi Treg/Tfh, CXCR5 + PD-1 lo Treg/Th17, and CXCR5 + PD-1 hi Treg/Th17 cells ( 43 , 150 , 152 ).…”

Section: Th1-related Inflammatory Cytokinesmentioning

confidence: 99%

“…After following up IL-2-treated SLE patients at the 24th week, the SRI-4 response rate was 65.52%, and 53.85% SLE patients had complete remission ( 153 ). Interestingly, comparing the advantage of prednisone treatment of SLE patients and prednisone+IL-2 treatment of SLE patients, it was found that 36.36% patients had a reduced proportion of Treg cells upon prednisone treatment, and prednisone treatment downregulated the Foxp3 expression in CD4 + T cells and the expression of CD39, ICOS, Bcl-2, and STAT5 in CD4 + Foxp3 + Treg cells ( 149 ). Prednisone+IL-2 treatment did not downregulate the number of Treg cells whereas it downregulated the SLEDAI score, upregulated the expression of C3 and C4, and improved rash and fever ( 149 ).…”

Section: Th1-related Inflammatory Cytokinesmentioning

confidence: 99%

“…Interestingly, comparing the advantage of prednisone treatment of SLE patients and prednisone+IL-2 treatment of SLE patients, it was found that 36.36% patients had a reduced proportion of Treg cells upon prednisone treatment, and prednisone treatment downregulated the Foxp3 expression in CD4 + T cells and the expression of CD39, ICOS, Bcl-2, and STAT5 in CD4 + Foxp3 + Treg cells ( 149 ). Prednisone+IL-2 treatment did not downregulate the number of Treg cells whereas it downregulated the SLEDAI score, upregulated the expression of C3 and C4, and improved rash and fever ( 149 ). For IL-2 treatment of LN patients, low-dose human IL-2 in treatment of active LN patients improved nephritis, achieved a higher remission rate as compared with placebo, and promoted the proliferation of Treg cells ( 154 ).…”

Section: Th1-related Inflammatory Cytokinesmentioning

confidence: 99%

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Th1-related transcription factors and cytokines in systemic lupus erythematosus

Tang,

Wang,

Chen

et al. 2023

Front. Immunol.

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Systemic lupus erythematosus (SLE) is an inflammatory disorder related to immunity dysfunction. The Th1 cell family including Th1 cells, transcription factor T-bet, and related cytokines IFNγ, TNFα, IL-2, IL-18, TGF-β, and IL-12 have been widely discussed in autoimmunity, such as SLE. In this review, we will comprehensively discuss the expression profile of the Th1 cell family in both SLE patients and animal models and clarify how the family members are involved in lupus development. Interestingly, T-bet-related age-associated B cells (ABCs) and low-dose IL-2 treatment in lupus were emergently discussed as well. Collection of the evidence will better understand the roles of the Th1 cell family in lupus pathogenesis, especially targeting IL-2 in lupus.

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Low-dose IL-2 mitigates glucocorticoid-induced Treg impairment and promotes improvement of SLE

Cited by 7 publications

References 8 publications

Elevation of Metrnβ and Its Association with Disease Activity in Systemic Lupus Erythematosus

Elevation of Metrnβ and Its Association with Disease Activity in Systemic Lupus Erythematosus

Analysis of the role of serum IL-2R, IL-6, IL-8, IL-10, and TNF-α in the treatment of immune escape mechanisms in patients with minimal ma tumors

Th1-related transcription factors and cytokines in systemic lupus erythematosus

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