A Role for NOD2 in Intestinal Memory T cell Formation and Function
Bibliographic record
Abstract
Abstract Aberrant resident memory T cell (TRM) responses have been associated with increased intestinal inflammation and Crohn’s disease (CD) pathology in humans. Genetic mutations in NOD2 are associated with the highest risk of CD development. NOD2 has been shown to be critical for initiating adaptive immune responses at systemic sites. However, the role of NOD2 in establishing memory T cell responses in the intestine remains unclear. Using an acute model of LCMV infection, we interrogated the role of NOD2 in intestinal memory T cell generation and function. Littermate wildtype or NOD2-deficient mice were infected intraperitoneally with LCMV-Armstrong, and the intestinal T cell priming, effector, and memory T cell responses were profiled in the mesenteric lymph nodes (mLN) and small intestinal lamina propria (SILP). Augmented NOD2 signalling at homeostasis and during infection increased endogenous and LCMV-specific CD4+ T cell numbers in the mLN, but not in the spleen. This effect was due to a NOD2-dependent increase in T cell homing to the mLN. Furthermore, NOD2-deficiency resulted in decreased effector and memory T cell numbers in the SILP. This effect was associated with decreased memory T cell functions in NOD2-deficient mice during ex vivo and in vivo recall experiments. Taken together, our experiments suggest a role for NOD2 in mediating optimal T cell priming in the mesenteric lymph nodes, which later affects effector and memory T cell functions in the intestine.
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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 | 0.001 |
| 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".