Erythroid Atypical Chemokine Receptor 1 Deficiency Aggravates Immune-Mediated Kidney Disease
Bibliographic record
Abstract
KEY POINTS: Selective erythroid atypical chemokine receptor 1 deficiency exacerbated disease activity in experimental GN via changes of the myeloid lineage. Activated monocytes and profibrogenic phenotypes of macrophages underlaid the kidney phenotype observed in erythroid-silent individuals. Genetically modified mouse models showed pathomechanisms of kidney diseases in patients of West African ancestry with erythroid atypical chemokine receptor 1 deficiency. BACKGROUND: Single-nucleotide polymorphisms of the atypical chemokine receptor 1 ( ACKR1 ) gene encode human Duffy antigen blood groups. Most individuals of West African ancestry carry a single-nucleotide polymorphism in the promoter region of the ACKR1 gene that disrupts its transcription in erythroid cells but not in venular endothelial cells, leading to an erythroid-silent, FyBES Duffy phenotype. METHODS: We used two mouse models of erythroid-selective ACKR1 deficiency to delineate the fundamental role of this receptor in the erythroid compartment in regulating the development of experimental immune-mediated kidney disease. RESULTS: Humanized transgenic Duffy erythroid-silent Duffy-negative transgene mice and chimeric wild-type mice transplanted with ACKR1-deficient bone marrow, both selectively lacking erythroid ACKR1, showed increased disease activity and fibrosis after induction of nephrotoxic serum nephritis, as compared with their respective controls. Mice lacking erythroid ACKR1 exhibited altered serum chemokine levels and bone marrow monocytes displaying activated and promigratory phenotypes. Moreover, they showed an increase in kidney-infiltrating macrophages that were characterized by a profibrotic transcriptome signature. No changes in ACKR1 expression in kidney vascular endothelial cells were seen in erythroid ACKR1-deficient mice with or without nephrotoxic serum nephritis. CONCLUSIONS: Our data demonstrates that erythroid-specific ACKR1 deficiency led to an increased infiltration of the kidney by macrophages with an altered profibrotic phenotype in nephrotoxic serum nephritis, resulting in aggravated kidney disease.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".