Selective augmentation of intestinal immunity by CD22-dependent SHP-1 control of β <sub>7</sub> integrin expression
Bibliographic record
Abstract
Abstract The regulation of integrin expression and function controls interactions of immune cells and targets their trafficking locally and systemically. We show here that the tyrosine phosphatase SHP-1 is required for lymphocyte surface expression of the intestinal immune response-associated integrin β 7 , but not for β 1 or β 2 integrins. Viable motheaten mice deficient for SHP-1 have less β 7 on T cells and lack β 7 on B cells. SHP-1 function is targeted in B cells by the B cell specific lectin CD22 (Siglec-2), suggesting a potential role for CD22 in β 7 expression. CD22-deficiency on B cells phenocopies the effects of SHP-1 haplodeficiency. Mechanistically, we show that SHP-1 suppresses β 7 endocytosis: internalization of β 7 but not β 1 integrin is accelerated in SHP-1 +/− and CD22 −/− B cells. Moreover, mutations in CD22 cytoplasmic SHP1-binding ITIM sequences reduce α 4 β 7 comparably, and loss of CD22 lectin activity has an intermediate effect suggesting a model in which the CD22 ITIM sequences recruit SHP-1 to control β 7 expression. Integrin α 4 β 7 selectively contributes to cell interactions in intestinal immunity. Consistent with this, CD22 deficient and SHP-1 +/− B cells display reduced β 7 -dependent homing to gut associated Peyer’s patches (PP); and CD22-deficiency impairs intestinal but not systemic antibody responses and delays clearance of the gut pathogen rotavirus. The results define a novel role for SHP-1 in the differential control of leukocyte integrins and an unexpected integrin β 7 -specific role for CD22-SHP-1 interplay in mucosal immunity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".