Deficiency of RIPK3 (receptor-interacting protein kinase 3) in antigen-presenting cells dampens the pro-inflammatory T cell response following antigen presentation
Bibliographic record
Abstract
Abstract Study Objective We have previously shown that RIPK3 (receptor-interacting protein kinase 3)-deficient mice are protected from the development of an induced murine model of systemic lupus erythematosus (SLE). The development of SLE autoantibodies in this model is associated with the generation of an antigen-specific T cell response. We hypothesize that RIPK3-deficient antigen-presenting cells (APCs) are impaired in generation of a robust T cell response, thereby impacting induction of SLE in our murine model. Methods We performed a complete cellular immunophenotyping on mice deficient in RIPK3, compared with wild type C57BL/6 mice. We also assessed the function of RIPK3-deficient APCs in an in vitro antigen presentation assay using ovalbumin (OVA) and OVA-specific OT-II T cells. Results No major differences in immune cell composition and phenotype were identified between naïve RIPK3-deficient and WT mice. However, RIPK3-deficient bone marrow-derived dendritic cells (BMDCs) were found to produce lower levels of pro-inflammatory cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) following lipopolysaccharide (LPS) stimulation. Moreover, presentation of OVA by RIPK3-deficient BMDCs resulted in a lower proportion of interferon (IFN)-γ producing OT-II T cells, compared to antigen presentation by WT BMDCs. In contrast, T cell proliferation was similar whether antigen was presented by RIPK3-deficient or WT BMDCs. Conclusion Our results suggest that RIPK3 deficiency in APCs impacts antigen presentation to T cells, identifying a possible mechanism by which RIPK3-deficient mice are protected from induction of SLE.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".