دورية أكاديمية
NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model
العنوان: | NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model |
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المؤلفون: | Diego Pazos-Castro, Zulema Gonzalez-Klein, Alma Yuste Montalvo, Guadalupe Hernandez-Ramirez, Alejandro Romero-Sahagun, Vanesa Esteban, Maria Garrido-Arandia, Jaime Tome-Amat, Araceli Diaz-Perales |
المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-15 (2022) |
بيانات النشر: | Nature Portfolio, 2022. |
سنة النشر: | 2022 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | Abstract Allergic sensitization is initiated by protein and epithelia interaction, although the molecular mechanisms leading this encounter toward an allergic phenotype remain unknown. Here, we apply the two-hit hypothesis of inflammatory diseases to the study of food allergy sensitization. First, we studied the effects of long-term depilation in mice by analyzing samples at different time points. Several weeks of depilation were needed until clear immunological changes were evidenced, starting with upregulation of NLRP3 protein levels, which was followed by overexpression of Il1b and Il18 transcripts. Secondly, we assessed the effects of allergen addition (in this case, Pru p 3 in complex with its natural lipid ligand) over depilated skin. Systemic sensitization was evaluated by intraperitoneal provocation with Pru p 3 and measure of body temperature. Anaphylaxis was achieved, but only in mice sensitized with Prup3_complex and not treated with the NLRP3 inhibitor MCC950, thus demonstrating the importance of both hits (depilation + allergen addition) in the consecution of the allergic phenotype. In addition, allergen encounter (but not depilation) promoted skin remodeling, as well as CD45+ infiltration not only in the sensitized area (the skin), but across several mucosal tissues (skin, lungs, and gut), furtherly validating the systemization of the response. Finally, a low-scale study with human ILC2s is reported, where we demonstrate that Prup3_complex can induce their phenotype switch (↑CD86, ↑S1P1) when cultured in vitro, although more data is needed to understand the implications of these changes in food allergy development. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2045-2322 |
Relation: | https://doaj.org/toc/2045-2322 |
DOI: | 10.1038/s41598-022-07421-y |
URL الوصول: | https://doaj.org/article/08fdb498c2094ecc8569d317b889561a |
رقم الأكسشن: | edsdoj.08fdb498c2094ecc8569d317b889561a |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20452322 |
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DOI: | 10.1038/s41598-022-07421-y |