Etude du microenvironnement inflammatoire dans la lymphomagenèse gastrique induite par l’infection à Helicobacter pylori
Bibliographic record
Abstract
H. pylori colonizes the stomach of about half of the world population and induces a chronic inflammation named gastritis, most often asymptomatic but which may evolve towards more serious gastroduodenal pathologies including gastric MALT lymphoma (mucosa-associated lymphoid tissue) or GML. Although occurring in a very small number of infected subjects, it is now well demonstrated that GML’s development is directly caused by H. pylori infection. In this disease, H. pylori-antigenic chronic stimulation to the gastric mucosa leads to the recruitment of lymphocytes and maintains a monoclonal proliferation of B lymphocytes organizing into lymphoid follicles which are normally absent in the gastric mucosa. Therefore GML is part of an inflammatory continuum response to H. pylori. However, the mechanisms leading to this lymphoma are not clearly understood. Since bacterial virulence factors seem to play a minimal role, the study of host factors and in particular the study of the inflammatory microenvironment appears to be an interesting way to better understanding the pathogenesis of this lymphoma.In the first part, we looked at the molecular mechanisms that may be involved by studying the deregulation of microRNAs (miRNAs). Our results showed an up regulation of 4 miRNAs (miR-155, miR-150, miR-196 and miR-138) and a down-regulation of 2 miRNAs (miR-7 and miR-153) in human stomachs at the GML stage, globally different results from those previously obtained by the team in the d3Tx mouse model of GML. Except miR-138, deregulated miRNAs could act synergistically on multiple validated targets involved in a common anti-apoptotic signaling pathway promoting cell survival and B lymphocytes proliferation leading to the lymphomagenesis process.Some cytokines, such as the the APRIL cytokine, would play a leading role in GML pathogenesis. Thus, the team has developed a promising GML model based on transgenic mice with the human form of this cytokine (Tg-hAPRIL). In a second part, we therefore focused on the study of the polarization of the inflammatory response in this novel animal model, and validated these results in the gastric biopsies of GML patients. Our results showed the presence of a balanced gastric Th1, Th2 and T regulatory inflammatory response at the lymphoma stage, both in the Tg-hAPRIL mouse model and in humans. After confirming the gastric overexpression of the APRIL cytokine in patients with GML, we demonstrated, on the one hand, that the target cells of the APRIL cytokine were mainly B lymphocytes present within the lymphoid infiltrates, thus supporting the hypothesis according to which the APRIL cytokine would participate in uncontrolled B lymphocyte proliferation and, on the other hand that the APRIL-producing cells were rare eosinophils present in the tumor microenvironment, suggesting a pro-tumoral role of this cell type in gastric lymphomagenesis.To conclude, all of our results demonstrate that the inflammatory microenvironment is a key contributor to the development of GML.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".