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Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy

Food allergy is a growing public health problem with ~15 million people affected in the United States. In allergic food disease, IgE on mast cells bind to ingested antigens leading to the activation and degranulation of mast cells. Stem cell factor (SCF) is mast cell growth and activation factor tha...

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Autores principales: Ptaschinski, Catherine, Rasky, Andrew J., Fonseca, Wendy, Lukacs, Nicholas W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005333/
https://www.ncbi.nlm.nih.gov/pubmed/33786039
http://dx.doi.org/10.3389/fimmu.2021.604192
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author Ptaschinski, Catherine
Rasky, Andrew J.
Fonseca, Wendy
Lukacs, Nicholas W.
author_facet Ptaschinski, Catherine
Rasky, Andrew J.
Fonseca, Wendy
Lukacs, Nicholas W.
author_sort Ptaschinski, Catherine
collection PubMed
description Food allergy is a growing public health problem with ~15 million people affected in the United States. In allergic food disease, IgE on mast cells bind to ingested antigens leading to the activation and degranulation of mast cells. Stem cell factor (SCF) is mast cell growth and activation factor that is required for peripheral tissue mast cells. We targeted a specific isoform of SCF, the larger 248 amino acid form, that drives peripheral tissue mast cell differentiation using a specific monoclonal antibody in a model of food allergy. Ovalbumin sensitized and intragastrically challenged mice were monitored for symptoms of anaphylaxis including respiratory distress, diarrhea, and a reduction in body temperature. During the second week of challenges, allergic mice were injected with an antibody to block SCF248 or given IgG control. Mice treated with α-SCF248 had a decreased incidence of diarrhea and no reduction in body temperature suggesting a reduction in anaphylaxis compared to IgG control treated animals. Re-stimulated mesenteric lymph nodes indicated that α-SCF248 treated mice had decreased OVA-specific Th2 cytokine production compared to IgG control treated allergic animals. The reduction of food induced anaphylaxis was accompanied by a significant reduction in gut leak. The mesenteric lymph node cells were analyzed by flow cytometry and showed a decrease in the number of type 2 innate lymphoid cells in mice injected with α-SCF248. Morphometric enumeration of esterase+ mast cells demonstrated a significant reduction throughout the small intestine. Using a more chronic model of persistent food-induced anaphylaxis, short term therapeutic treatment with α-SCF248 during established disease effectively blocked food induced anaphylaxis. Together, these data suggest that therapeutically blocking SCF248 in food allergic animals can reduce the severity of food allergy by reducing mast cell mediated disease activation.
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spelling pubmed-80053332021-03-29 Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy Ptaschinski, Catherine Rasky, Andrew J. Fonseca, Wendy Lukacs, Nicholas W. Front Immunol Immunology Food allergy is a growing public health problem with ~15 million people affected in the United States. In allergic food disease, IgE on mast cells bind to ingested antigens leading to the activation and degranulation of mast cells. Stem cell factor (SCF) is mast cell growth and activation factor that is required for peripheral tissue mast cells. We targeted a specific isoform of SCF, the larger 248 amino acid form, that drives peripheral tissue mast cell differentiation using a specific monoclonal antibody in a model of food allergy. Ovalbumin sensitized and intragastrically challenged mice were monitored for symptoms of anaphylaxis including respiratory distress, diarrhea, and a reduction in body temperature. During the second week of challenges, allergic mice were injected with an antibody to block SCF248 or given IgG control. Mice treated with α-SCF248 had a decreased incidence of diarrhea and no reduction in body temperature suggesting a reduction in anaphylaxis compared to IgG control treated animals. Re-stimulated mesenteric lymph nodes indicated that α-SCF248 treated mice had decreased OVA-specific Th2 cytokine production compared to IgG control treated allergic animals. The reduction of food induced anaphylaxis was accompanied by a significant reduction in gut leak. The mesenteric lymph node cells were analyzed by flow cytometry and showed a decrease in the number of type 2 innate lymphoid cells in mice injected with α-SCF248. Morphometric enumeration of esterase+ mast cells demonstrated a significant reduction throughout the small intestine. Using a more chronic model of persistent food-induced anaphylaxis, short term therapeutic treatment with α-SCF248 during established disease effectively blocked food induced anaphylaxis. Together, these data suggest that therapeutically blocking SCF248 in food allergic animals can reduce the severity of food allergy by reducing mast cell mediated disease activation. Frontiers Media S.A. 2021-03-09 /pmc/articles/PMC8005333/ /pubmed/33786039 http://dx.doi.org/10.3389/fimmu.2021.604192 Text en Copyright © 2021 Ptaschinski, Rasky, Fonseca and Lukacs. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ptaschinski, Catherine
Rasky, Andrew J.
Fonseca, Wendy
Lukacs, Nicholas W.
Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy
title Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy
title_full Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy
title_fullStr Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy
title_full_unstemmed Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy
title_short Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy
title_sort stem cell factor neutralization protects from severe anaphylaxis in a murine model of food allergy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005333/
https://www.ncbi.nlm.nih.gov/pubmed/33786039
http://dx.doi.org/10.3389/fimmu.2021.604192
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