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NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model

Authors :
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
Source :
Scientific Reports, Vol 12, Iss 1, Pp 1-15 (2022)
Publication Year :
2022
Publisher :
Nature Portfolio, 2022.

Abstract

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.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
20452322
Volume :
12
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.08fdb498c2094ecc8569d317b889561a
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-022-07421-y