MerTK mediates T cell tolerance in the pancreatic islets during type 1 diabetes
Bibliographic record
Abstract
Abstract Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that results from destruction of the beta cells in the pancreatic islets. Curiously, infiltrated islets can continue to contain beta cells for years following disease onset, suggesting a tolerance checkpoint following islet infiltration. While T cells are required for T1D progression, other immune cell populations also infiltrate the islets, including CD11c+ antigen presenting cells (APCs). We depleted CD11c+ cells to determine their role in maintaining T cell tolerance in the islets. CD11c depletion resulted in increased CD8 T cell motility arrest and effector function. MerTK+ APCs have been associated with T cell tolerance induction following apoptotic cell uptake. We identified MerTK expression on a subset of islet-infiltrating CD11c+ APCs. To test if MerTK mediates T cell tolerance in the islets, we treated pre-diabetic non-obese diabetic (NOD) and non-autoimmune C57BL/6 mice with a MerTK/Flt3 inhibitor. Blood glucose remained normal in C57BL/6 mice. However, in 50% of NOD mice with pre-existing islet infiltration, MerTK/Flt3 inhibition resulted in extremely rapid diabetes onset. The rapid disease onset occurred prior to Flt3-dependent population shifts in the islets, suggesting a MerTK rather than Flt3 mediated effect. Within 24 hours of MerTK inhibition, islet-antigen specific CD4 and CD8 T cells arrested motility in the islets, and CD8 T cell activation increased in the islets. Thus, inhibition of MerTK signaling resulted in a break in T cell tolerance and rapid islet destruction. These results suggest that CD11c+ APCs are involved in a MerTK-dependent tolerance checkpoint during T1D, which maintains T cell tolerance in the islets following islet infiltration.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".