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Ndfip1 mediates peripheral tolerance to self and exogenous antigen by inducing cell cycle exit in responding CD4+ T cells

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, January 2014
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Title
Ndfip1 mediates peripheral tolerance to self and exogenous antigen by inducing cell cycle exit in responding CD4+ T cells
Published in
Proceedings of the National Academy of Sciences of the United States of America, January 2014
DOI 10.1073/pnas.1322739111
Pubmed ID
Authors

John A. Altin, Stephen R. Daley, Jason Howitt, Helen J. Rickards, Alison K. Batkin, Keisuke Horikawa, Simon J. Prasad, Keats A. Nelms, Sharad Kumar, Lawren C. Wu, Seong-Seng Tan, Matthew C. Cook, Christopher C. Goodnow

Abstract

The NDFIP1 (neural precursor cell expressed, developmentally down-regulated protein 4 family-interacting protein 1) adapter for the ubiquitin ligase ITCH is genetically linked to human allergic and autoimmune disease, but the cellular mechanism by which these proteins enable foreign and self-antigens to be tolerated is unresolved. Here, we use two unique mouse strains--an Ndfip1-YFP reporter and an Ndfip1-deficient strain--to show that Ndfip1 is progressively induced during T-cell differentiation and activation in vivo and that its deficiency causes a cell-autonomous, Forkhead box P3-independent failure of peripheral CD4(+) T-cell tolerance to self and exogenous antigen. In small cohorts of antigen-specific CD4(+) cells responding in vivo, Ndfip1 was necessary for tolerogen-reactive T cells to exit cell cycle after one to five divisions and to abort Th2 effector differentiation, defining a step in peripheral tolerance that provides insights into the phenomenon of T-cell anergy in vivo and is distinct from the better understood process of Bcl2-interacting mediator of cell death-mediated apoptosis. Ndfip1 deficiency precipitated autoimmune pancreatic destruction and diabetes; however, this depended on a further accumulation of nontolerant anti-self T cells from strong stimulation by exogenous tolerogen. These findings illuminate a peripheral tolerance checkpoint that aborts T-cell clonal expansion against allergens and autoantigens and demonstrate how hypersensitive responses to environmental antigens may trigger autoimmunity.

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X Demographics

The data shown below were collected from the profiles of 2 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 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Mexico 1 3%
Denmark 1 3%
Unknown 35 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 24%
Researcher 6 16%
Student > Bachelor 4 11%
Student > Master 4 11%
Student > Doctoral Student 3 8%
Other 8 22%
Unknown 3 8%
Readers by discipline Count As %
Immunology and Microbiology 14 38%
Agricultural and Biological Sciences 8 22%
Medicine and Dentistry 5 14%
Biochemistry, Genetics and Molecular Biology 1 3%
Nursing and Health Professions 1 3%
Other 1 3%
Unknown 7 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 15 February 2014.
All research outputs
#15,537,011
of 24,625,114 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#89,545
of 101,438 outputs
Outputs of similar age
#184,670
of 317,494 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#717
of 948 outputs
Altmetric has tracked 24,625,114 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 101,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.8. This one is in the 10th percentile – i.e., 10% 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 317,494 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 948 others from the same source and published within six weeks on either side of this one. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.