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Record W4390064057 · doi:10.1016/j.cell.2023.11.027

Sensory neurons promote immune homeostasis in the lung

2023· article· en· W4390064057 on OpenAlexaff
Masato Tamari, Kate L. Del Bel, Aaron Ver Heul, Lydia Zamidar, Keisuke Orimo, Masato Hoshi, Anna M. Trier, Hiroshi Yano, Ting-Lin Yang, Catherine M. Biggs, Kenichiro Motomura, Rintaro Shibuya, Chuyue Yu, Zili Xie, Hisato Iriki, Zhen Wang, Kelsey Auyeung, Gargi Damle, Deniz Demircioğlu, Jill Gregory, Dan Hasson, Jinye Dai, Rui B. Chang, Hideaki Morita, Kenji Matsumoto, Sanjay Jain, Steven J. Van Dyken, Joshua D. Milner, Dusan Bogunovic, Hongzhen Hu, David Artis, Stuart E. Turvey, Brian Kim

Bibliographic record

VenueCell · 2023
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsBC Children's HospitalUniversity of British Columbia
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Center for Complementary and Integrative HealthNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNational Institute on Alcohol Abuse and AlcoholismNational Institutes of HealthInternational Center for Genetic Engineering and BiotechnologyNational Center for Child Health and DevelopmentLEO PharmaJapanese Society of AllergologyCrohn's and Colitis FoundationPaul G. Allen Family FoundationIcahn School of Medicine at Mount SinaiNational Heart, Lung, and Blood InstitutePfizerDoris Duke Charitable Foundation
KeywordsBiologyHomeostasisSensory systemImmune systemLungNeuroscienceImmunologyCell biologyInternal medicine

Abstract

fetched live from OpenAlex

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant ( JAK1 GoF ) into mice and observed the development of spontaneous AD-like skin disease but unexpected resistance to lung inflammation when JAK1 GoF expression was restricted to the stroma. We identified a previously unrecognized role for JAK1 in vagal sensory neurons in suppressing airway inflammation. Additionally, expression of Calcb /CGRPβ was dependent on JAK1 in the vagus nerve, and CGRPβ suppressed group 2 innate lymphoid cell function and allergic airway inflammation. Our findings reveal evolutionarily conserved but distinct functions of JAK1 in sensory neurons across tissues. This biology raises the possibility that therapeutic JAK inhibitors may be further optimized for tissue-specific efficacy to enhance precision medicine in the future.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.667
Threshold uncertainty score0.442

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 studies0.0000.000
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 head0.019
GPT teacher head0.271
Teacher spread0.253 · 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 designObservational
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

Citations117
Published2023
Admission routes1
Has abstractyes

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