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L'apport de l'étude des mécanismes intracellulaires pour l'évaluation du pouvoir sensibilisant de substances industrielles

Abstract : Allergies are among the most frequent occupational diseases. Its most common manifestations are respiratory or cutaneous. Allergy is defined as a hypersensitivity reaction that takes place in two phases: a sensitization phase, which is asymptomatic, and a response or trigger phase, which is symptomatic. This pathology is associated with exposure to so-called "sensitizing" substances. The detection of sensitizing substances is based on in chemico or in vitro tests. Contrary to skin sensitization, there are no validated tests to assess the respiratory sensitizing potential. In this context, a mouse bone marrow-derived dendritic cell model has been developed to assess sensitizing potential. It allows to evaluate the sensitizing potential but it is not able to discriminate a skin sensitizer from a respiratory sensitizer. In order to optimize and improve this test, signalling pathways involved in sensitization have been studied in order to identify interesting markers that could be integrated into the model and to study the mechanisms involved in sensitization. The study of the MAPK and STAT pathways showed the p38 MAPK to be activated for all sensitizers tested. In addition, the Nrf2/Keap1 pathway seems to be involved in the DC response to sensitizers and by further studying this pathway, we showed that the p38 MAPK pathway positively regulates the activation of this pathway. The study of the mechanisms provides interesting information on the mechanism of respiratory sensitization and offers promising markers that can be integrated into the BMDC model, which could allow it in the future in combination with other tests to distinguish a skin sensitizer from a respiratory sensitizer.
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Submitted on : Thursday, October 6, 2022 - 4:10:23 PM
Last modification on : Friday, October 7, 2022 - 11:41:00 AM


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  • HAL Id : tel-03800852, version 1


Adrien Audry. L'apport de l'étude des mécanismes intracellulaires pour l'évaluation du pouvoir sensibilisant de substances industrielles. Médecine humaine et pathologie. Université de Lorraine, 2022. Français. ⟨NNT : 2022LORR0082⟩. ⟨tel-03800852⟩



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