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Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis

2008· article· en· W3175142890 on OpenAlexafffundabout
Itay Shalev, Hao Liu, Cheryl Koscik, Agata Bartczak, Mojib Javadi, Kit Man Wong, Asif Maknojia, Wei He, Ming Feng Liu, Jun Diao, Erin Winter, Justin Manuel, Doug McCarthy, Jennifer L. Gommerman, Mark S. Cattral, David A. Clark, James Phillips, Reginald R. Gorczynski, Li Zhang, Greg Downey, David Grant, Myron I. Cybulsky, Gary Levy

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldMedicine
TopicCell Adhesion Molecules Research
Canadian institutionsUniversity of Toronto
FundersHeart and Stroke Foundation of Canada
KeywordsImmunologyAntibodyAutoimmune diseaseBiology

Abstract

fetched live from OpenAlex

Mice with targeted deletion of fibrinogen‐like protein 2 ( fgl2 ) spontaneously developed autoimmune glomerulonephritis with increasing age, as did wild‐type recipients reconstituted with fgl2 −/− bone marrow. These data implicate FGL2 as an important immunoregulatory molecule and led us to identify the underlying mechanisms. Deficiency of FGL2, produced by CD4 + CD25 + regulatory T cells (Treg), resulted in increased T cell proliferation to lectins and alloantigens, T helper 1 (Th1) polarization, and increased numbers of antibody‐producing B cells following immunization with T‐independent antigens. Dendritic cells (DC) were more abundant in fgl2 −/− mice and had increased expression of CD80 and MHCII following LPS stimulation. Treg cells were also more abundant in fgl2 −/− mice, but their suppressive activity was significantly impaired. Antibody to FGL2 completely inhibited Treg cell activity in vitro . FGL2 inhibited DC maturation and induced apoptosis of B cells through binding to the low affinity FcγRIIB receptor. Collectively, these data suggest that FGL2 contributes to Treg cell activity and inhibits the development of autoimmune disease. This work was supported in part by grants from the Heart and Stroke Foundation of Canada and the Canadian Institutes for Health Research.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.267
Teacher spread0.242 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations12
Published2008
Admission routes3
Has abstractyes

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Same venueThe FASEB JournalSame topicCell Adhesion Molecules ResearchFrench-language works237,207