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VISTA deficiency attenuates antibody-induced arthritis and alters macrophage gene expression in response to simulated immune complexes

Overview of attention for article published in Arthritis Research & Therapy, December 2017
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Title
VISTA deficiency attenuates antibody-induced arthritis and alters macrophage gene expression in response to simulated immune complexes
Published in
Arthritis Research & Therapy, December 2017
DOI 10.1186/s13075-017-1474-y
Pubmed ID
Authors

Sabrina Ceeraz, Susan K. Eszterhas, Petra A. Sergent, David A. Armstrong, Alix Ashare, Thomas Broughton, Li Wang, Dov Pechenick, Christopher M. Burns, Randolph J. Noelle, Matthew P. Vincenti, Roy A. Fava

Abstract

In addition to activated T cells, the immune checkpoint inhibitor "V domain-containing Ig suppressor of T-cell activation" (VISTA) is expressed by myeloid cell types, including macrophages and neutrophils. The importance of VISTA expression by myeloid cells to antibody-induced arthritis and its potential for relevance in human disease was evaluated. VISTA was immunolocalized in normal and arthritic human synovial tissue sections and synovial tissue lysates were subjected to western blot analysis. The collagen antibody-induced arthritis model (CAIA) was performed with DBA/1 J mice treated with antibodies against VISTA and with VISTA-deficient mice (V-KO). Total mRNA from arthritic joints, spleens, and cultured macrophages was analyzed with NanoString arrays. Cytokines secreted by splenic inflammatory macrophages were determined. In-vitro chemotaxis and signal transduction assays were performed with cultured macrophages. VISTA protein was localized to synovial membrane cells, neutrophils, and scattered cells in lymphocyte-rich foci and was detected by western blot analysis in normal synovium and synovium from rheumatoid arthritis patients. Deficiency of VISTA or treatment of mice with anti-VISTA monoclonal antibodies attenuated CAIA. Joint damage and MMP-3 expression were significantly reduced in V-KO mice. Surface expression of C5a receptor was reduced on monocytes, neutrophils, and cultured macrophages from V-KO. Upon Fc receptor engagement in vitro, gene expression by V-KO macrophages was altered profoundly compared to WT, including a significant induction of IL-1 receptor antagonist (IL1rn). VISTA expression supports immune-complex inflammation in CAIA and VISTA is expressed in human synovium. VISTA supports optimal responses to C5a and modulates macrophage responses to immune complexes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 18%
Student > Ph. D. Student 5 13%
Other 4 10%
Student > Bachelor 3 8%
Student > Master 3 8%
Other 6 15%
Unknown 11 28%
Readers by discipline Count As %
Immunology and Microbiology 6 15%
Biochemistry, Genetics and Molecular Biology 4 10%
Engineering 4 10%
Medicine and Dentistry 3 8%
Business, Management and Accounting 1 3%
Other 7 18%
Unknown 14 36%
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 14 December 2017.
All research outputs
#20,006,062
of 25,450,869 outputs
Outputs from Arthritis Research & Therapy
#2,820
of 3,387 outputs
Outputs of similar age
#321,852
of 446,092 outputs
Outputs of similar age from Arthritis Research & Therapy
#44
of 50 outputs
Altmetric has tracked 25,450,869 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 3,387 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 14th percentile – i.e., 14% 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 446,092 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 50 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.