Perinatal Programming of Mucosal Stromal Cell Identity by the Lymphotoxin Pathway Regulates Mucosal Immune Responses in the Adult
Bibliographic record
Abstract
ABSTRACT Redundant mechanisms support IgA responses to intestinal antigens. These include multiple priming sites (mesenteric lymph nodes (MLN), Peyer’s patches and isolated lymphoid follicles) and various cytokines that promote class switch to IgA, even in the absence of T cells. In spite of these back-up mechanisms, vaccination against enteric pathogens such as Rotavirus has limited success in some populations. Genetic and environmental signals experienced during early life are known to influence mucosal immunity, yet the mechanisms for how these exposures operate remain unclear. Here we used Rotavirus infection to follow antigen-specific IgA responses through time and in different gut compartments. Using genetic and pharmacological approaches, we tested the role of a pathway known to support IgA responses (Lymphotoxin – LT) at different developmental stages. We found that LT-beta receptor (LTβR) signalling in utero programs intestinal IgA responses in adulthood by affecting antibody class switch recombination to IgA and subsequent generation of IgA antibody-secreting cells within an intact MLN. In addition, in utero LTβR signalling dictates the phenotype and function of MLN stromal cells in order to support IgA responses in the adult. Collectively, our studies uncover new mechanistic insights into how in utero LTβR signalling impacts mucosal immune responses during adulthood. One Sentence Summary Early life LTβR signalling is critical for programming the mesenteric lymph node stromal cell environment, impacting both antibody isotype switching to IgA and the differentiation of IgA + antibody secreting cells. Graphic Abstract
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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) | 0.043 | 0.004 |
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".