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Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD

Overview of attention for article published in Inflammatory Bowel Diseases, November 2017
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Title
Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD
Published in
Inflammatory Bowel Diseases, November 2017
DOI 10.1097/mib.0000000000001270
Pubmed ID
Authors

Dror S. Shouval, Liza Konnikova, Alexandra E. Griffith, Sarah M. Wall, Amlan Biswas, Lael Werner, Moran Nunberg, Jochen Kammermeier, Jeremy A. Goettel, Rajsavi Anand, Hannah Chen, Batia Weiss, Jian Li, Anthony Loizides, Baruch Yerushalmi, Tadahiro Yanagi, Rita Beier, Laurie S. Conklin, Christen L. Ebens, Fernanda G. M. S. Santos, Mary Sherlock, Jeffery D. Goldsmith, Daniel Kotlarz, Sarah C. Glover, Neil Shah, Athos Bousvaros, Holm H. Uhlig, Aleixo M. Muise, Christoph Klein, Scott B. Snapper

Abstract

IL10 receptor (IL10R) deficiency causes severe infantile-onset inflammatory bowel disease. Intact IL10R-dependent signals have been shown to be important for innate and adaptive immune cell functions in mice. We have previously reported a key role of IL10 in the generation and function of human anti-inflammatory macrophages. Independent of innate immune cell defects, the aim of the current study was to determine the role of IL10R signaling in regulating human CD4 T-cell function. Peripheral blood mononuclear cells and intestinal biopsies cells were collected from IL10/IL10R-deficient patients and controls. Frequencies of CD4 T-cell subsets, naive T-cell proliferation, regulatory T cell (Treg)-mediated suppression, and Treg and TH17 generation were determined by flow cytometry. Transcriptional profiling was performed by NanoString and quantitative real-time polymerase chain reaction. RNA in situ hybridization was used to determine the quantities of various transcripts in intestinal mucosa. Analysis of 16 IL10- and IL10R-deficient patients demonstrated similar frequencies of peripheral blood and intestinal Tregs, compared with control subjects. In addition, in vitro Treg suppression of CD4 T-cell proliferation and generation of Treg were not dependent on IL10R signaling. However, IL10R-deficient T naive cells exhibited higher proliferative capacity, a strong TH17 signature, and an increase in polarization toward TH17 cells, compared with controls. Moreover, the frequency of TH17 cells was increased in the colon and ileum of IL10R-deficient patients. Finally, we show that stimulation of IL10R-deficient Tregs in the presence of IL1β leads to enhanced production of IL17A. IL10R signaling regulates TH17 polarization and T-cell proliferation in humans but is not required for the generation and in vitro suppression of Tregs. Therapies targeting the TH17 axis might be beneficial for IL10- and IL10R-deficient patients as a bridge to allogeneic hematopoietic stem cell transplantation.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 53 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 17%
Researcher 9 17%
Student > Master 9 17%
Student > Bachelor 5 9%
Professor > Associate Professor 4 8%
Other 6 11%
Unknown 11 21%
Readers by discipline Count As %
Medicine and Dentistry 13 25%
Immunology and Microbiology 8 15%
Agricultural and Biological Sciences 6 11%
Biochemistry, Genetics and Molecular Biology 4 8%
Computer Science 2 4%
Other 5 9%
Unknown 15 28%
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 26 October 2017.
All research outputs
#17,292,294
of 25,382,440 outputs
Outputs from Inflammatory Bowel Diseases
#2,769
of 3,732 outputs
Outputs of similar age
#217,828
of 340,752 outputs
Outputs of similar age from Inflammatory Bowel Diseases
#42
of 66 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,732 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 19th percentile – i.e., 19% 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 340,752 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.