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Human TSLP and OX40L as targets of therapeutic intervention for allergic asthma

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Novel therapeutic targets for asthma

Asthma is a significant source of morbidity worldwide and most often emerges during early childhood. A European study aimed to investigate the immune mechanisms driving asthma development by recapitulating the human asthmatic immune system in mouse models.

Health

Allergic asthma is an inflammatory disease of the respiratory system caused by allergens such as house dust mites (HDMs). Research evidence indicates that in response to allergens, bronchial epithelial cells produce thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33. These instruct dendritic cells — the professional antigen-presenting cells of the immune system — to activate T helper-2 (Th2) immune responses and cause chronic inflammation. The key objective of the EU-funded TSLP IN ASTHMA project was to investigate the therapeutic outcome of intervening with any of these allergen-induced cytokines. To this end, researchers used a 'humanised' mouse — whose immune system was reconstituted by cells from asthma patients. Scientists observed high levels of TSLP and IL-33 in these animals, with the latter playing an important role in neonatal mice. Young animals also demonstrated high levels of the IL-33 receptor (T1/ST2) in lung dendritic cells and innate lymphoid cells. Antibody blocking of the dendritic cell OX40L receptor or the IL-33 receptor in neonatal mice during sensitisation or allergen challenge showed a significant reduction in asthma manifestation. These results validated the initial concept of using this pathway to treat or prevent allergic asthma. Although clinical validation is required, TSLP IN ASTHMA outcomes will have significant medical implications as they could be translated to prevent or treat childhood asthma. This would reduce the enormous financial burden incurred by asthma patients and concurrently improve their quality of life.

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29 November 2022