Th2 Differentiation in Distinct Lymph Nodes Influences the Site of Mucosal Th2 Immune-Inflammatory Responses
Bibliographic record
Abstract
Allergic individuals rarely present with concurrent multiple-organ disease but, rather, with manifestations that privilege a specific site such as the lung, skin, or gastrointestinal tract. Whether the site of allergic sensitization influences the localization of Th2 immune-inflammatory responses and, ultimately, the organ-specific expression of disease, remains to be determined. In this study, we investigated whether both the site of initial Ag exposure and concomitant Th2 differentiation in specific lymph nodes (LNs) privileges Th2 memory responses to mucosal and nonmucosal sites, and whether this restriction is associated with a differential expression in tissue-specific homing molecules. In mice exposed to Ag (OVA) via the peritoneum, lung, or skin, we examined several local and distal LNs to determine the site of Ag-specific proliferation and Th2 differentiation. Whereas respiratory and cutaneous Ag exposure led to Ag-specific proliferation and Th2 differentiation exclusively in lung- and skin-draining LNs, respectively, Ag delivery to the peritoneum evoked responses in gut-associated, as well as distal thoracic, LNs. Importantly, only mice that underwent Th2 differentiation in thoracic- or gut-associated LNs mounted Th2 immune-inflammatory responses upon respiratory or gastric Ag challenge, respectively, whereas cutaneous Th2 recall responses were evoked irrespective of the site of initial sensitization. In addition, we observed the differential expression of gut homing molecules (CCR9, alpha(4), beta(7)) in gut-associated LNs and, unexpectedly, a universal induction of skin-related homing molecules (CCR4, CCR10) in all LNs. These data suggest that the site of initial Th2 differentiation and differential homing molecule expression restricts Th2 immune-inflammatory responses to mucosal, but not cutaneous, tissues.
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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) | 0.001 | 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".