Novel Role of Lewis A Glycans in Regulating Neutrophil Trafficking
Bibliographic record
Abstract
Pathogen‐triggered neutrophil (PMN) recruitment is critical for innate immunity, but aberrant PMN influx is also implicated in the pathogenesis of numerous inflammatory diseases of the gut and lungs. Fucosylated terminal glycans from the Lewis glycan family, such as Lewis‐x (Le x ) and Sialyl Lewis‐x, have previously been implicated in the regulation of important PMN functions, including Selectin‐mediated PMN transendothelial trafficking. While such glycans based on the type 2 sequence (Galb1‐4GlcNAc‐R) are abundant on PMNs, the presence of type 1 Galb1‐3GlcNAc‐R glycans required for the expression of Lewis‐a (Le a ) have not yet been reported. Here, we conclusively report that Le a is expressed in human PMNs as probed using mAbs whose specificity was confirmed using glycan array technology. Le a function was further probed using Le a ‐selective mAbs and a Le a binding lectin resulting in increased PMN chemotaxis and migration across model intestinal epithelia. Analyses of glycan synthetic machinery in PMN revealed expression of a b1–3 Galactosyltransferase and an α1–4 Fucosyltransferase, glycosyltransferases that are required for Le a synthesis. Specificity of findings to Le a was confirmed by absence of antibody‐mediated effects using PMN from individuals deficient in α1–4 fucosylation. These results suggest that PMN expression of Le a has important functional consequences that may be relevant during PMN trafficking within inflamed mucosal tissues. We therefore propose that PMN Le a represents a new target for regulating intestinal innate immunity and modulating inflammation in diseases where dysregulated PMN influx is associated with bystander tissue damage. Furthermore, differential responses of human PMN to physiological ligands of Le a (based on an individuals Lewis phenotype) may provide insights into the mechanisms linking specific Lewis phenotypes with differential susceptibilities to bacterial infections, viral infections and coronary heart disease. Support or Funding Information NIH ‐ RO1 DK072564‐21 (Parkos) CCFA ‐ Career Development Award (314660) (Brazil)
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".