MO238: Erythroid ACKR1 Expression has a Protective Effect on the Development of Experimental Glomerulonephritis
Bibliographic record
Abstract
Abstract BACKGROUND AND AIMS The overwhelming majority of individuals of West African ancestry carry an ‘erythroid silent’ FyB(ES) SNP in the promoter region of ACKR1 that causes a selective loss of ACKR1 in erythroid cells but does not affect its expression in endothelial cells. The FyB(ES) polymorphism is of a special interest for understanding human kidney disease as individuals of West African ancestry have higher incidence of chronic kidney disease. Moreover, multiple chemokine ligands of ACKR1 are known to contribute to the inflammatory pathology in experimental nephrotoxic serum nephritis (NTS), a murine model of immune complex glomerulonephritis. METHOD We developed two humanized transgenic mouse strains that are genetically deficient for mouse ACKR1 but instead carry either West African FyB(ES) or Caucasian FyB human polymorphic ACKR1 variants. These strains as well as ACKR1-deficient and WT mice were subjected to NTS. The parameters of immunopathogenesis and kidney disease were evaluated after 14 days after the induction of NTS. RESULTS Albuminuria, PAS and tubular injury scores were significantly increased in FyB(ES)tg and ACKR1-deficient mice as compared with their respective control strains. While monocytes were unchanged in peripheral blood, we found significantly increased numbers of macrophages and neutrophils infiltrating the kidneys of FyB(ES)tg and ACKR1-deficient mice. Interestingly, T cell numbers in the draining lymph nodes were comparable between FyB(ES)tg and ACKR1-deficient mice and their respective controls. CONCLUSION We found that NTS was more severe in ACKR1-deficient and FyB(ES) mice as compared with their respective controls. Our results show that ACKR1 expression in the erythroid compartment has a significant impact on the development of kidney disease. These findings have important implications for the pathomechanisms of glomerulonephritis in individuals of West African ancestry who lack ACKR1 selectively in the erythroid lineage.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
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".