Development of Integrated Approaches to Testing and Assessment for respiratory sensitization based on the AOP

Author : Takao Ashikaga, Izuru Mizoguchi, Takayuki Yoshimoto

Abstract :The development of in vitro respiratory sensitisation tests demands an understanding of the mechanisms by which chemicals cause respiratory sensitisation. The recently proposed adverse outcome pathway (AOP) for sensitisation of the respiratory tract is useful for gaining such an understanding. The Th2 response induced by a respiratory sensitiser may be related to signals from the airway epithelium, which is known to secrete cytokines (e.g. interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP)) that instruct Dendritic Cells (DCs) to mature; these cytokines also drive Th2 polarisation by upregulating the expression levels of co-stimulatory markers such as OX40L in DCs. Therefore, in vitro methods that involve the coculture of DCs and airway epithelial cells could be useful for recapitulating in vitro the immune responses specific to respiratory sensitisation. Using this co-culture system named DCsens, respiratory senseitisers, skin sensitisers and nons sensitisers were selected from existing information and predictability was simulated using in vitro test results. This hybrid evaluation system by adding DCsens to the existing in vitro skin sensitization tests showed the possibility of classifying chemicals into each group

Keywords :respiratory sensitisation, in vitro testing, DCsens, Th2 response, cytokines

Conference Name :International Conference on Stem Cell and Organoid Biology (ICSCOB-25)

Conference Place Oslo,Norway

Conference Date 25th Nov 2025