Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjögren’s syndrome

Miao, Miao; Hao, Zhenye; Guo, Yingying; Zhang, Xiaoying; Zhang, Shengxiao; Luo, Jing; Zhao, Xiangcong; Zhang, Chen; Liu, Xiaoqing; Wu, Xiongfei; Xu, Dan; Zhao, Jinfang; Lu, Xue-Chun; Gao, Chong; Li, Xiaofeng

doi:10.1136/annrheumdis-2018-213036

Cited by 93 publications

(67 citation statements)

References 10 publications

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“…Non-severe adverse events were characterized by skin rashes at the injection site that could heal Discussion CD4 + CD25 + FOXP3 + T cells, also known as Tregs, can modulate the immune system, maintain selftolerance and immunological homeostasis, and suppress the proliferation of effector T cells and the production of pro-in ammatory cytokines and autoantibodies. In human and animal studies, dysfunction or reduction of circulating Tregs has been observed in autoimmune diseases, including systemic lupus erythematosus 20 , dermatomyositis/polymyositis (DM/PM) 16 , primary Sjögren's syndrome (pSS) 17 , and RA 21 22 . However, results from several studies regarding the levels of peripheral Tregs in RA are controversial 23 .…”

Section: Changes In Disease Activity Parameters and General Biochemicmentioning

confidence: 99%

“…Indeed, the role of IL-2 (as an immunomodulatory cytokine) in the function and differentiation of CD4 + T lymphocyte subsets, especially Tregs with high expression of IL-2Rα, has been the focus of extensive studies on immunemediated diseases in vitro or in vivo 9 14 . Our previous studies found the e cacy and safety of low-dose IL-2 targeted regulation of Tregs levels in patients with psoriatic arthritis (PsA) 15 , dermatomyositis/polymyositis (DM/PM) 16 , primary Sjögren's syndrome (pSS) 17 . However, evidence of the clinical e cacy and safety of IL-2 combined treatment in patients with RA is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Low-Dose IL-2 Therapy Limits the Reduction in Absolute Numbers of Circulating Regulatory T Cells in Rheumatoid Arthritis

Zhang

Wang

et al. 2020

Preprint

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Background Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4+T subsets and the clinical feasibility of IL-2 therapies in patients with RA.Methods The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment of at 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment.Results RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs (P < 0.05). Patients treated with low-dose IL-2 had a three-fold increase in absolute anti-inflammatory Treg counts, as well as a two-fold increase in the other CD4+T subsets. Moreover, post-treatment levels of markers of disease activity in RA patients treated with IL-2 were significantly lower than the baseline values (P < 0.001), with no apparent side effects.Conclusions Decreased absolute counts of circulating CD4+T lymphocyte subsets were observed in patients with RA. Circulating Tregs, which mediate immune tolerance, may be involved in the pathogenesis and progression of RA; however, this was ameliorated by low-dose IL-2, without obvious side effects.

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Section: Changes In Disease Activity Parameters and General Biochemicmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low-Dose IL-2 Therapy Limits the Reduction in Absolute Numbers of Circulating Regulatory T Cells in Rheumatoid Arthritis

Zhang

Wang

et al. 2020

Preprint

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“…But there was no significant improvement in clinical manifestations in a short time when comparing combinational treatment of IL‐2 and classical drugs with classical therapy. No obvious adverse reactions were observed . The following (Table ) lists the clinical studies related to low‐dose IL‐2 in the treatment of rheumatic immune diseases.…”

Section: Low‐dose Il‐2 In the Treatment Of Rheumatic Immune Diseasesmentioning

confidence: 99%

“…No obvious adverse reactions were observed. 81 The following (Table 1) lists the clinical studies related to low-dose IL-2 in the treatment of rheumatic immune diseases.…”

Section: Low-dose Il-2 For Pssmentioning

confidence: 99%

Progress in interleukin‐2 therapy for rheumatic immune diseases by regulating the immune balance of T cells

Shao

Gao

2019

Scand J Immunol

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Breaking the balance between effector T cells, including Th17 (T helper cell 17) cells, and regulatory T cells (Tregs) is a key link in the pathogenesis of rheumatic immune diseases, which lead to a new concept of regulating immune balance in the treatment of rheumatic immune diseases. Interleukin (IL)‐2 can effectively regulate the differentiation, development and functional activity of regulatory T cells, thus restoring the immune balance between regulatory T cells and effector T cells. Therefore, low‐dose IL‐2 has been used in the treatment of rheumatic immune diseases, and it has become a promising new choice to achieve therapeutic purpose by regulating the immune balance of T cell. Here, we discuss the role of T cells immune imbalance in the pathogenesis of rheumatic immune diseases and the mechanism of IL‐2 in the treatment of rheumatic immune diseases by regulating T cells immune balance and summarize the relevant clinical trials.

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“…The 16S rRNA in the stool specimens were sequenced using the Roche/45 high-throughput sequencing platform. The absolute numbers of circulating lymphocytes and CD4+ T subgroups of these individuals were detected by flow cytometry combined with standard absolute counting beads 5…”

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The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus

et al. 2019

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Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjögren’s syndrome

Cited by 93 publications

References 10 publications

Low-Dose IL-2 Therapy Limits the Reduction in Absolute Numbers of Circulating Regulatory T Cells in Rheumatoid Arthritis

Low-Dose IL-2 Therapy Limits the Reduction in Absolute Numbers of Circulating Regulatory T Cells in Rheumatoid Arthritis

Progress in interleukin‐2 therapy for rheumatic immune diseases by regulating the immune balance of T cells

The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus

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