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The impact of age and gut microbiota on Th17 and Tfh cells in K/BxN autoimmune arthritis

Overview of attention for article published in Arthritis Research & Therapy, August 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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1 blog
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7 X users

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Title
The impact of age and gut microbiota on Th17 and Tfh cells in K/BxN autoimmune arthritis
Published in
Arthritis Research & Therapy, August 2017
DOI 10.1186/s13075-017-1398-6
Pubmed ID
Authors

Fei Teng, Krysta M. Felix, C. Pierce Bradley, Debdut Naskar, Heqing Ma, Walid A. Raslan, Hsin-Jung Joyce Wu

Abstract

Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis. Comparing young and middle-aged K/BxN T cells of the same TCR specificity allows us to study T cells with an age focus eliminating a key variable: TCR repertoire alteration with age. In addition to joints, we also studied pathological changes in the lung, an important extra-articular RA manifestation. We used flow cytometry to evaluate T follicular helper (Tfh) and T helper 17 (Th17) cells, as they both contribute to autoantibody production, a key disease index in both RA and K/BxN arthritis. Middle-aged K/BxN mice had aggravated arthritis and pathological changes in the lung compared to young mice. Middle-aged mice displayed a strong accumulation of Tfh but not Th17 cells, and had defective Th17 differentiation and low expression of interleukin-23, a critical cytokine for Th17 maintenance. Although a soaring Tfh cell population accompanied by robust germinal center B cell responses were found in middle-aged mice, there was decreased cycling of Tfh cells, and SFB only induced the non-Tfh cells to upregulate Bcl-6, the Tfh master transcription factor, in the young but not the middle-aged group. Finally, the accumulated Tfh cells in middle-aged mice had an effector phenotype (CD62L(lo)CD44(hi)). Age-dependent Tfh cell accumulation may play a crucial role in the increased autoimmune disease phenotype in middle-age. SFB, a potent stimulus for inducing Tfh differentiation, fails to promote Tfh differentiation in middle-aged K/BxN mice, suggesting that most of the middle-aged Tfh cells with an effector phenotype are Tfh effector memory cells induced at an earlier age. Our results also indicate that exposure to immunomodulatory commensals may allow the young host to develop an overactive immune system reminiscent of that found in the middle-aged host.

X Demographics

X Demographics

The data shown below were collected from the profiles of 7 X users 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 78 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 78 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 15%
Student > Doctoral Student 10 13%
Student > Bachelor 10 13%
Student > Master 9 12%
Student > Ph. D. Student 8 10%
Other 11 14%
Unknown 18 23%
Readers by discipline Count As %
Immunology and Microbiology 21 27%
Medicine and Dentistry 13 17%
Agricultural and Biological Sciences 8 10%
Biochemistry, Genetics and Molecular Biology 5 6%
Nursing and Health Professions 4 5%
Other 7 9%
Unknown 20 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 07 May 2018.
All research outputs
#3,055,597
of 25,382,440 outputs
Outputs from Arthritis Research & Therapy
#620
of 3,380 outputs
Outputs of similar age
#53,736
of 326,133 outputs
Outputs of similar age from Arthritis Research & Therapy
#9
of 51 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,380 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one has done well, scoring higher than 81% of its peers.
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 326,133 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 51 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.