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IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients

Overview of attention for article published in Frontiers in immunology, August 2018
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Title
IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients
Published in
Frontiers in immunology, August 2018
DOI 10.3389/fimmu.2018.01755
Pubmed ID
Authors

Jing Luo, Bingxia Ming, Cai Zhang, Xiaofei Deng, Pingfei Li, Zhengping Wei, Yu Xia, Kan Jiang, Hong Ye, Wanli Ma, Zheng Liu, Huabin Li, Xiang-Ping Yang, Lingli Dong

Abstract

To investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren's syndrome (pSS) patients. This study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation. We found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4+ T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3. Our findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 15%
Student > Master 3 9%
Researcher 3 9%
Student > Doctoral Student 2 6%
Student > Postgraduate 2 6%
Other 4 12%
Unknown 15 44%
Readers by discipline Count As %
Medicine and Dentistry 9 26%
Immunology and Microbiology 6 18%
Agricultural and Biological Sciences 2 6%
Unspecified 1 3%
Computer Science 1 3%
Other 3 9%
Unknown 12 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 September 2018.
All research outputs
#19,954,338
of 25,385,509 outputs
Outputs from Frontiers in immunology
#22,587
of 31,537 outputs
Outputs of similar age
#249,656
of 341,279 outputs
Outputs of similar age from Frontiers in immunology
#495
of 635 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,537 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,279 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 635 others from the same source and published within six weeks on either side of this one. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.