Distinct sustained structural and functional effects of interleukin-33 and interleukin-25 on the airways in a murine asthma surrogate

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Abstract

Interleukin-25 (IL-25) and IL-33, which belong to distinct cytokine families, induce and promote T helper type 2 airway inflammation. Both cytokines probably play a role in asthma, but there is a lack of direct evidence to clarify distinctions between their functions and how they might contribute to distinct 'endotypes' of disease. To address this, we made a direct comparison of the effects of IL-25 and IL-33 on airway inflammation and physiology in our established murine asthma surrogate, which involves per-nasal, direct airway challenge. Intranasal challenge with IL-33 or IL-25 induced inflammatory cellular infiltration, collagen deposition, airway smooth muscle hypertrophy, angiogenesis and airway hyper-responsiveness, but neither increased systemic production of IgE or IgG1. Compared with that of IL-25, the IL-33-induced response was characterized by more sustained laying down of extracellular matrix protein, neoangiogenesis, T helper type 2 cytokine expression and elevation of tissue damping. Hence, both IL-25 and IL-33 may contribute significantly and independently to asthma 'endotypes' when considering molecular targets for the treatment of human disease.

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Li, Y., Wang, W., Huang, P., Zhang, Q., Yao, X., Wang, J., … Ying, S. (2015). Distinct sustained structural and functional effects of interleukin-33 and interleukin-25 on the airways in a murine asthma surrogate. Immunology, 145(4), 508–518. https://doi.org/10.1111/imm.12465

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