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Record W2587237894 · doi:10.1093/ecco-jcc/jjx002.213

P087 Increased wnt ligands expression in M2c macrophages is associated with fibrosis in Stat6 knockout mice

2017· article· en· W2587237894 on OpenAlexfundno aff
D Ortiz‐Masiá, Pedro Salvador, Dulce C. Macias-Ceja, Laura Gisbert-Ferrándiz, Carlos Hernández, Sara Calatayud, Juan V. Esplugues, M D Barrachina

Bibliographic record

VenueJournal of Crohn s and Colitis · 2017
Typearticle
Languageen
FieldMedicine
TopicEosinophilic Esophagitis
Canadian institutionsnot available
FundersDairy Farmers of Canada
KeywordsMacrophage polarizationWnt signaling pathwayCD86CD16MacrophageFlow cytometrySTAT6FibrosisIntestinal mucosaPopulationImmunologyPathologyMedicineChemistryMolecular biologyInterleukin 4BiologyIn vitroInternal medicineCytokineSignal transductionT cellImmune systemCell biologyCD3Biochemistry

Abstract

fetched live from OpenAlex

Background: STAT6 plays a crucial role in M2a macrophage polarization in vitro and these cells mediate mucosal healing in an acute model of TNBS-colitis through the expression of Wnt ligands [1]. We have recently reported that STAT6 deficiency favours fibrosis in a murine model of TNBS colitis [2] and we aim to characterize here the functional relevance of the macrophage phenotype in fibrosis development. Methods: WT or STAT6(−/−) mice were given TNBs (0.5, 0.5, 0.75, 0.75, 1, and 1 mg, intrarectally) or saline weekly and they were sacrificed 3, 5 or 7 weeks after the first TNBs administration. The percentage of CD206, CD16, and CD86 positive cells was analyzed by flow cytometry in F4/80+ macrophages isolated from the intestinal mucosa. The mRNA expression of Wnt ligands was evaluated in F4/80+ CD16+ macrophages isolated from the mucosa, 7 weeks after the first TNBs administration and results are expressed as fold induction vs vehicle-treated mice. Data are expressed as mean ± SEM with n≥8 in all groups (*p<0.05). Results: TNBs increased the percentage of CD206 positive macrophages in the mucosa of TNBS-WT animals while it failed to do that in TNBS-STAT6(−/−) mice. The percentage of CD16 positive macrophages increased in a time-dependent manner only in the mucosa of STAT6(−/−)-TNBS-treated mice. The number of CD86+ cells was similar in TNBS-WT and TNBS-STAT6(−/−) mice. Figure 1. Macrophages population. In CD16+ macrophages isolated from TNBS-STAT6(−/−) mice the mRNA expression of canonical and non-canonical Wnt ligands was significantly increased compared with cells isolated from TNBS-WT mice. Table 1. Wnt ligands Conclusions: An increased percentage of M2c macrophages which exhibited an increased expression of Wnt ligands is detected in the mucosa of TNBS-STAT6 knockout mice and it could mediate the increased fibrosis detected in these animals. References: [1] Cosín-Roger J, Ortiz-Masiá D, Calatayud S, Hernández C, Esplugues JV, Barrachina MD., (2016), The activation of Wnt signaling by a STAT6-dependent macrophage phenotype promotes mucosal repair in murine IBD., Mucosal Immunol. 2016 Jul;9(4):986–98. doi: 10.1038/mi.2015.123. [2] P. Salvador, (2016), STAT6 deficiency alters macrophage polarization and promotes fibrosis in a murine model of chronic inflammation. ECCO2016

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 score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0060.002

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 head0.012
GPT teacher head0.272
Teacher spread0.260 · 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".

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Citations0
Published2017
Admission routes1
Has abstractyes

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