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Record W3131054438 · doi:10.1038/s41590-021-00862-z

A CD22–Shp1 phosphatase axis controls integrin β7 display and B cell function in mucosal immunity

2021· article· en· W3131054438 on OpenAlexaff
Romain Ballet, Martin Brennan, Carolin Brandl, Ningguo Feng, Jeremy Berri, Julian Cheng, Borja Ocón, Amin Alborzian Deh Sheikh, Alex Márki, Yuhan Bi, Clare L. Abram, Clifford A. Lowell, Takeshi Tsubata, Harry B. Greenberg, Matthew S. Macauley, Klaus Ley, Lars Nitschke, Eugene C. Butcher

Bibliographic record

VenueNature Immunology · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Tyrosine Phosphatases
Canadian institutionsUniversity of Alberta
FundersNational Institute of Allergy and Infectious DiseasesNational Heart, Lung, and Blood InstituteU.S. Department of Health and Human ServicesNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungDeutsche ForschungsgemeinschaftMinistry of Education, Culture, Sports, Science and TechnologyCrohn's and Colitis FoundationJapan Society for the Promotion of ScienceCrohn's and Colitis Foundation of AmericaU.S. Department of Veterans AffairsFundación Ramón Areces
KeywordsCD22Lymphocyte homing receptorEndocytosisCell biologyHigh endothelial venulesHoming (biology)BiologyB cellIntegrinCD49bProtein tyrosine phosphataseLymphocyteMolecular biologyT cellCell adhesionCellImmunologyPhosphorylationBiochemistryImmune systemAntigen-presenting cellAntibody

Abstract

fetched live from OpenAlex

The integrin α4β7 selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissue (GALT). Here, we describe unexpected involvement of the tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec-2) in the regulation of α4β7 surface expression and gut immunity. Shp1 selectively inhibited β7 endocytosis, enhancing surface α4β7 display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid–dependent manner with integrin β7 on the cell surface to target intracellular Shp1 to β7. Shp1 restrained plasma membrane β7 phosphorylation and inhibited β7 endocytosis without affecting β1 integrin. B cells with reduced Shp1 activity, lacking CD22 or expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface α4β7 and in homing to GALT. Consistent with the specialized role of α4β7 in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses. Lymphocyte homing to the gut and Peyer’s patches requires expression of integrin α4β7. Ballet and colleagues report that B cell expression of CD22 is required to specifically retain surface expression of β7 integrin molecules, thereby promoting B cell retention in the gut and optimal gut mucosal antibody responses.

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 score0.316
Threshold uncertainty score0.962

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 integrity0.0010.001
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 head0.003
GPT teacher head0.222
Teacher spread0.219 · 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

Citations31
Published2021
Admission routes1
Has abstractyes

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