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Record W4414568094 · doi:10.1101/2025.09.24.678140

Nicotinic acetylcholine receptor signaling regulates cytokine production in Jurkat T cells

2025· preprint· en· W4414568094 on OpenAlexafffund
Bailey Laforest, Alain R. Simard

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicNicotinic Acetylcholine Receptors Study
Canadian institutionsLaurentian UniversityCarleton University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsJurkat cellsNicotinic agonistT cellCytokineRegulatorNicotineSignal transductionImmune systemReceptor

Abstract

fetched live from OpenAlex

Abstract Nicotinic acetylcholine receptors (nAChRs) regulate immune cell functions, yet their expression patterns and roles in human T cells remain incompletely defined. The immunomodulatory effects of α7 nAChR signaling in human immune cells is complicated by the presence of the human-specific duplicated α7 (dupα7) subunit. Here, we investigated the expression and function of nAChRs in human Jurkat T cells, focusing on α7, dupα7, α9, and α10. Quantitative PCR revealed transcripts for all four subunits. Mitogenic stimulation with PMA, ionomycin, and ConA significantly downregulated α7, α9, and α10 expression while upregulating dupα7, suggesting dynamic remodeling of receptor composition during T cell activation. Functional assays showed that α7 antagonism with ArIB[V11L,V16D] strongly suppressed mitogen-induced IL-2 and TNF-α secretion, while nicotine pretreatment produced more modest reductions. Flow cytometry confirmed a decreased frequency of IL-2+ cells following treatment with nicotine or nAChR antagonists. These findings establish Jurkat cells as a tractable model for studying nAChR signaling in human T cells. Our results demonstrate that α7-containing nAChRs positively regulate cytokine production, while dupα7 expression increases during activation and may act as a negative regulator of α7 function. Together, these data highlight nAChRs as key modulators of T cell activity and identify α7 and dupα7 as potential therapeutic targets for regulating adaptive immunity.

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 score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.002

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 head0.009
GPT teacher head0.232
Teacher spread0.223 · 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

Citations0
Published2025
Admission routes2
Has abstractyes

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