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Record W2912344179 · doi:10.1126/science.aat7186

Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

2019· article· en· W2912344179 on OpenAlexaff
Joep Grootjans, Niklas Krupka, Shuhei Hosomi, Juan D. Matute, Thomas Hanley, Svetlana Saveljeva, Thomas Gensollen, Jarom Heijmans, Hai Li, Julien Limenitakis, Stephanie C. Ganal‐Vonarburg, Shengbao Suo, Adrienne Luoma, Yosuke Shimodaira, Jinzhi Duan, David Q. Shih, Margaret E. Conner, Jonathan N. Glickman, Gwenny M. Fuhler, Noah W. Palm, Marcel R. de Zoete, C. Janneke van der Woude, Guo‐Cheng Yuan, Kai W. Wucherpfennig, Stephan R. Targan, Philip Rosenstiel, Richard A. Flavell, Kathy D. McCoy, Andrew J. Macpherson, Arthur Kaser, Richard S. Blumberg

Bibliographic record

VenueScience · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsUniversity of Calgary
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Diabetes and Digestive and Kidney DiseasesPediatric Scientist Development ProgramNational Cancer InstituteEuropean Research CouncilHarvard Digestive Diseases Center, Harvard UniversityJapan Foundation for Applied EnzymologyNational Institutes of HealthNIH Office of the DirectorJapan Society for the Promotion of ScienceEvelyn TrustDeutsche ForschungsgemeinschaftNational Institute for Health and Care ResearchCrohn's and Colitis FoundationNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustWellcomeNational Institute of Allergy and Infectious DiseasesHoward Hughes Medical Institute
KeywordsEndoplasmic reticulumUnfolded protein responseImmunoglobulin ALamina propriaInflammationImmunologyAutophagyCell biologyAntibodyBiologyTight junctionSecretory IgAImmunoglobulin GEpitheliumChemistryApoptosisBiochemistry

Abstract

fetched live from OpenAlex

Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.

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 score0.001
Threshold uncertainty score0.003

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 communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.007
GPT teacher head0.231
Teacher spread0.224 · 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

Citations64
Published2019
Admission routes1
Has abstractyes

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