Critical role for the microbiota in limiting inflammatory intestinal T cell responses
Bibliographic record
Abstract
Abstract Efficient functioning of the intestine and intestinal immune system depends on interactions between the host and microbiota. Breakdown in these interactions leads to reduced ability to respond to intestinal pathogens along with increased intestinal inflammation which together can lead to pathologic inflammatory conditions such as inflammatory bowel disease. While a number of intestinal immune cells are likely regulated by the microbiota, we have found critical regulation of intestinal antigen presenting cells (APCs) expressing the chemokine receptor, CX3CR1. CX3CR1+ APCs are able to secrete both pro- and anti-inflammatory cytokines and are capable of mediating intestinal protection or pathology. Using in vivo models, we identified a regulatory loop whereby intestinal CX3CR1+ APCs reduced induction of Th1 cells against intestinal pathogens and promoted generation of regulatory T cells against soluble food antigens and the microbiota itself. This regulatory response depends on anti-inflammatory cytokine IL-10 production by CX3CR1+ APCs. Disruption of the intestinal microbiota switched the functional capacity of CX3CR1+ APCs so they now drove inflammatory Th1 responses and mediated pathology in a model of colitis. Mechanistically, we determined that epithelial attachment by intestinal microbes was required to turn on anti-inflammatory functions by CX3CR1+ APCs. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes homeostasis. Our study demonstrates the potential therapeutic benefits of microbiota and host immune cell manipulation with the goal of amplifying or inhibiting intestinal T cell responses.
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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) | 0.002 | 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".