Shp1 regulates T cell homeostasis by antagonizing IL-4 signalling (P1312)
Bibliographic record
Abstract
Abstract The tyrosine phosphatase Shp1 is expressed ubiquitously in hematopoietic cells and is generally viewed as a negative regulator. Null mutations in Ptpn6, which encodes Shp1, result in the motheaten phenotype, characterized by widespread inflammation that causes death by 3-4 weeks of age. Previous studies of motheaten mice identified Shp1 as a negative regulator of TCR signaling, but the severe inflammation in these mice could have confounded our understanding of Shp1 function in T cell biology. To define the T cell intrinsic role of Shp1, we have characterized T cell-specific conditional knockout mice. Surprisingly, we detect no changes in TCR responsiveness in Shp1-deficient thymocytes or peripheral T cells. Instead, T cell Shp1 KO mice are enriched for memory-phenotype T-cells that express elevated levels of CD44 in the periphery. In addition, activated Shp1-deficient CD4+ T cells skew to Th2 and produce elevated levels of IL-4. Following IL-4 stimulation, Stat 6 activation is sustained in Shp1 deficient T-cells, leading to enhanced IL-4 production. Elimination of IL-4, through in vivo administration of a neutralizing antibody or by crossing to IL-4 KO mice, results in marked reduction of the excessive memory-like population in T cell specific Shp1 KO mice. Therefore, Shp1 is an essential negative regulator of IL-4 signaling in and is critical for the maintainance of T cell homeostasis.
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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 | 0.001 |
| 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".