NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model
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.
Main Authors: | , , , , , , , , |
---|---|
Other Authors: | |
Format: | artículo biblioteca |
Language: | English |
Published: |
Nature Publishing Group
2022-02-28
|
Online Access: | http://hdl.handle.net/10261/272740 http://dx.doi.org/10.13039/100010784 http://dx.doi.org/10.13039/501100003759 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/100012818 https://api.elsevier.com/content/abstract/scopus_id/85125601611 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
dig-inia-es-10261-272740 |
---|---|
record_format |
koha |
institution |
INIA ES |
collection |
DSpace |
country |
España |
countrycode |
ES |
component |
Bibliográfico |
access |
En linea |
databasecode |
dig-inia-es |
tag |
biblioteca |
region |
Europa del Sur |
libraryname |
Biblioteca del INIA España |
language |
English |
description |
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. |
author2 |
Ministerio de Economía y Competitividad (España) |
author_facet |
Ministerio de Economía y Competitividad (España) Pazos-Castro, Diego Gonzalez-Klein, Zulema Montalvo, Alma Yuste Hernandez-Ramirez, Guadalupe Romero-Sahagun, Alejandro Esteban, Vanesa Garrido-Arandía, María Tome-Amat, Jaime Díaz-Perales, Araceli |
format |
artículo |
author |
Pazos-Castro, Diego Gonzalez-Klein, Zulema Montalvo, Alma Yuste Hernandez-Ramirez, Guadalupe Romero-Sahagun, Alejandro Esteban, Vanesa Garrido-Arandía, María Tome-Amat, Jaime Díaz-Perales, Araceli |
spellingShingle |
Pazos-Castro, Diego Gonzalez-Klein, Zulema Montalvo, Alma Yuste Hernandez-Ramirez, Guadalupe Romero-Sahagun, Alejandro Esteban, Vanesa Garrido-Arandía, María Tome-Amat, Jaime Díaz-Perales, Araceli NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model |
author_sort |
Pazos-Castro, Diego |
title |
NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model |
title_short |
NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model |
title_full |
NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model |
title_fullStr |
NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model |
title_full_unstemmed |
NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model |
title_sort |
nlrp3 priming due to skin damage precedes ltp allergic sensitization in a mouse model |
publisher |
Nature Publishing Group |
publishDate |
2022-02-28 |
url |
http://hdl.handle.net/10261/272740 http://dx.doi.org/10.13039/100010784 http://dx.doi.org/10.13039/501100003759 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/100012818 https://api.elsevier.com/content/abstract/scopus_id/85125601611 |
work_keys_str_mv |
AT pazoscastrodiego nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT gonzalezkleinzulema nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT montalvoalmayuste nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT hernandezramirezguadalupe nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT romerosahagunalejandro nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT estebanvanesa nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT garridoarandiamaria nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT tomeamatjaime nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel AT diazperalesaraceli nlrp3primingduetoskindamageprecedesltpallergicsensitizationinamousemodel |
_version_ |
1802819633516904448 |
spelling |
dig-inia-es-10261-2727402024-05-14T20:45:49Z NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model Pazos-Castro, Diego Gonzalez-Klein, Zulema Montalvo, Alma Yuste Hernandez-Ramirez, Guadalupe Romero-Sahagun, Alejandro Esteban, Vanesa Garrido-Arandía, María Tome-Amat, Jaime Díaz-Perales, Araceli Ministerio de Economía y Competitividad (España) Instituto de Salud Carlos III European Commission Comunidad de Madrid Universidad Politécnica de Madrid Banco Santander Pazos-Castro, Diego [0000-0002-0686-5131] Gonzalez-Klein, Zulema [0000-0003-3762-3781] Montalvo, Alma Yuste [0000-0002-4727-1284] Hernandez-Ramirez, Guadalupe [0000-0003-3031-6754] Romero-Sahagun, Alejandro [0000-0002-9417-8293] Garrido-Arandía, María [0000-0001-6114-5754] Tome-Amat, Jaime [0000-0003-4442-3649] Díaz-Perales, Araceli [0000-0002-1093-3627] 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. This research was funded by the Spanish Government (MINECO, grant BIO2017-84548- R); Instituto de Salud Carlos III (ISCIII) co-founded by FEDER Thematic Networks and Cooperative Research Centers: ARADYAL (RD16/0006/0003; RD16/0006/0013) and the Community of Madrid (FOODAL-CM_S2018/BAAA-4574). DPC was funded by Universidad Politécnica de Madrid and Banco Santander with a predoctoral Programa Propio grant. ARS was funded from the Community of Madrid included in the project FOOD-AL (FOODAL-CM_S2018/BAAA-4574). GHR was funded by European Comission (H2020-NMBP-X-KET-2017-768641—AllerScreening). JTA was funded from Instituto de Salud Carlos III (ISCIII) co-founded by FEDER Thematic Networks and Cooperative Research Centers: ARADYAL (RD16/0006/0003). Peer reviewed 2022-06-16T12:48:53Z 2022-06-16T12:48:53Z 2022-02-28 artículo http://purl.org/coar/resource_type/c_6501 Scientific Reports 12: 3329 (2022) 2045-2322 http://hdl.handle.net/10261/272740 10.1038/s41598-022-07421-y http://dx.doi.org/10.13039/100010784 http://dx.doi.org/10.13039/501100003759 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/100012818 35228630 2-s2.0-85125601611 https://api.elsevier.com/content/abstract/scopus_id/85125601611 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2017-84548-R/ES/ESTUDIO DEL PAPEL DE LOS LIGANDOS LIPIDICOS TRANSPORTADOS POR ALERGENOS EN LA SENSIBILIZACION ALERGICA/ info:eu-repo/grantAgreement/MINECO//RD16%2F0006%2F0013/ES/Asma, Reacciones Adversas y Alérgicas (ARADYAL)/ S2018/BAAA-4574/FOODAL info:eu-repo/grantAgreement/EC/H2020/768641 info:eu-repo/grantAgreement/EC/RD16/0006/0003/ARADYAL Scientific Reports Publisher's version https://doi.org/10.1038/s41598-022-07421-y Sí open Nature Publishing Group |