Aging in the absence of TLR2 is associated with reduced IFN-γ responses in the large intestine and increased severity of induced colitis
Bibliographic record
Abstract
Age-associated changes in immune function and their implications for intestinal inflammation are poorly understood. Defects in innate immunity have been shown to enhance intestinal inflammation and have been demonstrated upon aging. This study aimed to determine the consequences of aging in the presence and absence of TLR2 on intestinal inflammation. Young and aged (>60 weeks), control C57Bl/6 and TLR2-deficient (TLR2(-/-)) mice were examined. The cecum and mid-colon were analyzed for tissue damage, cytokine profiles, and trefoil factor 3 (TFF3) expression at baseline or after 5 days of treatment with dextran sodium sulfate (DSS) and 5 or 13 days recovery. Untreated, aged TLR2(-/-) mice had no significant intestinal inflammation but had reduced colonic IFN-gamma and IL-10 compared with younger mice. Aged TLR2(-/-) mice developed more severe colitis than other groups, as indicated by histological examination and overall weight loss. There were significant increases in colonic IFN-gamma following DSS treatment in young but not in aged mice. TFF3 was substantially reduced in the cecum and increased in the colon of aged but not younger TLR2(-/-) mice following DSS treatment. These results demonstrate that even upon aging, TLR2-deficient animals did not develop intestinal disease. However, they failed to respond appropriately to an inflammatory insult, and the consequences of this were most severe in aged animals. Cytokine and TFF3 changes associated with aging may contribute to more severe intestinal inflammation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".