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Record W4409802149 · doi:10.1016/j.immuni.2025.04.002

B cell-derived acetylcholine promotes liver regeneration by regulating Kupffer cell and hepatic CD8+ T cell function

2025· article· en· W4409802149 on OpenAlexafffund
Nastaran Fazel Modares, Liam D. Hendrikse, Logan K. Smith, Michael St. Paul, Jillian Haight, Ping Luo, Shaofeng Liu, Jérôme Fortin, Frances Tong, Andrew Wakeham, Soode Moghadas Jafari, Chunxing Zheng, Robert Flick, Jennifer Silvester, Thorsten Berger, Troy Ketela, Simone Helke, Erica Foffi, Raheleh Niavarani, Mary Saunders, Isabelle Colonna, Bruna Araújo David, Tashi Rastogi, Woo‐Yong Lee, Paul Kubes, Tak W. Mak

Bibliographic record

VenueImmunity · 2025
Typearticle
Languageen
FieldNeuroscience
TopicVagus Nerve Stimulation Research
Canadian institutionsQueen's UniversityMcGill UniversityUniversity of CalgaryUniversity Health NetworkUniversity of TorontoPrincess Margaret Cancer Centre
FundersCanadian Institutes of Health ResearchInnovation and Technology CommissionCancer Research Institute
KeywordsKupffer cellBiologyCell biologyFunction (biology)Regeneration (biology)T cellCellCD8Liver regenerationImmunologyImmune systemBiochemistry

Abstract

fetched live from OpenAlex

<h2>Summary</h2> Liver regeneration (LR) is essential for recovery from acute trauma, cancer surgery, or transplantation. Neurotransmitters such as acetylcholine (ACh) play a role in LR by stimulating immune cells and augmenting hepatocyte proliferation, but the source of this ACh remains unclear. Here, we demonstrated that B cells expressing choline acetyltransferase (ChAT), which synthesizes ACh, were required for LR. Mice lacking ChAT<sup>+</sup> B cells subjected to partial hepatectomy (PHX) displayed greater mortality due to failed LR. Kupffer cells and hepatic CD8<sup>+</sup> T cells expressed the α7 nicotinic ACh receptor (nAChR), and LR was disrupted in mice lacking α7 nAChR. Mechanistically, B cell-derived ACh signaled through α7 nAChR to positively regulate the function of regenerative Kupffer cells and to control the activation of hepatic CD8<sup>+</sup> T cells to curtail harmful interferon-gamma (IFNγ) production. Our work offers insights into LR mechanisms that may point to therapies for liver damage.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.064
Threshold uncertainty score0.750

Codex and Gemma teacher scores by category

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

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 head0.031
GPT teacher head0.285
Teacher spread0.254 · 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 teacher head, 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

Citations20
Published2025
Admission routes2
Has abstractyes

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