Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.

Food allergies, and peanut allergy in particular, are leading causes of anaphylactic fatalities worldwide. The immune mechanisms that underlie food allergy remain ill-defined and controversial, in part because studies in humans typically focus on analysis of a limited number of prototypical Th1/Th2...

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Autores principales:	Jungang Xie, Larisa C Lotoski, Rishma Chooniedass, Ruey-Chyi Su, F Estelle R Simons, Joel Liem, Allan B Becker, Jude Uzonna, Kent T HayGlass
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dc96061906fd4b90a42cd3dbd1da01ed
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spelling	oai:doaj.org-article:dc96061906fd4b90a42cd3dbd1da01ed2021-11-18T08:12:25ZElevated antigen-driven IL-9 responses are prominent in peanut allergic humans.1932-620310.1371/journal.pone.0045377https://doaj.org/article/dc96061906fd4b90a42cd3dbd1da01ed2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23071516/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Food allergies, and peanut allergy in particular, are leading causes of anaphylactic fatalities worldwide. The immune mechanisms that underlie food allergy remain ill-defined and controversial, in part because studies in humans typically focus on analysis of a limited number of prototypical Th1/Th2 cytokines. Here we determine the kinetics and prevalence of a broad panel of peanut-driven cytokine and chemokine responses in humans with current peanut allergy vs those with stable, naturally occurring clinical tolerance to peanut. Our primary focus is identification of novel indicators of immune dysregulation. Antigen-specific cytokine mRNA and protein responses were elicited in primary culture via peanut or irrelevant antigen (Leishmania extract, milk antigens) mediated stimulation of fresh peripheral blood cells from 40 individuals. Peanut extract exposure in vitro induced a broad panel of responses associated with Th2/Th9-like, Th1-like and Th17-like immunity. Peanut-dependent Type 2 cytokine responses were frequently found in both peanut allergic individuals and those who exhibit clinical tolerance to peanut ingestion. Among Th2/Th9-associated cytokines, IL-9 responses discriminated between allergic and clinically tolerant populations better than did commonly used IL-4, IL-5 or IL-13 responses. Comparison with responses evoked by unrelated control antigen-mediated stimulation showed that these differences are antigen-dependent and allergen-specific. Conversely, the intensity of IL-12, IL-17, IL-23 and IFN-γ production was indistinguishable in peanut allergic and peanut tolerant populations. In summary, the ability to generate and maintain cytokine responses to peanut is not inherently distinct between allergic and peanut tolerant humans. Quantitative differences in the intensity of cytokine production better reflects clinical phenotype, with optimally useful indicators being IL-9, IL-5, IL-13 and IL-4. Equivalent, and minimal, Ag-dependent pro-inflammatory cytokine levels in both healthy and peanut allergic volunteers argues against a key role for such cytokines in maintenance of clinical tolerance to food antigens in humans.Jungang XieLarisa C LotoskiRishma ChooniedassRuey-Chyi SuF Estelle R SimonsJoel LiemAllan B BeckerJude UzonnaKent T HayGlassPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e45377 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jungang Xie Larisa C Lotoski Rishma Chooniedass Ruey-Chyi Su F Estelle R Simons Joel Liem Allan B Becker Jude Uzonna Kent T HayGlass Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.
description	Food allergies, and peanut allergy in particular, are leading causes of anaphylactic fatalities worldwide. The immune mechanisms that underlie food allergy remain ill-defined and controversial, in part because studies in humans typically focus on analysis of a limited number of prototypical Th1/Th2 cytokines. Here we determine the kinetics and prevalence of a broad panel of peanut-driven cytokine and chemokine responses in humans with current peanut allergy vs those with stable, naturally occurring clinical tolerance to peanut. Our primary focus is identification of novel indicators of immune dysregulation. Antigen-specific cytokine mRNA and protein responses were elicited in primary culture via peanut or irrelevant antigen (Leishmania extract, milk antigens) mediated stimulation of fresh peripheral blood cells from 40 individuals. Peanut extract exposure in vitro induced a broad panel of responses associated with Th2/Th9-like, Th1-like and Th17-like immunity. Peanut-dependent Type 2 cytokine responses were frequently found in both peanut allergic individuals and those who exhibit clinical tolerance to peanut ingestion. Among Th2/Th9-associated cytokines, IL-9 responses discriminated between allergic and clinically tolerant populations better than did commonly used IL-4, IL-5 or IL-13 responses. Comparison with responses evoked by unrelated control antigen-mediated stimulation showed that these differences are antigen-dependent and allergen-specific. Conversely, the intensity of IL-12, IL-17, IL-23 and IFN-γ production was indistinguishable in peanut allergic and peanut tolerant populations. In summary, the ability to generate and maintain cytokine responses to peanut is not inherently distinct between allergic and peanut tolerant humans. Quantitative differences in the intensity of cytokine production better reflects clinical phenotype, with optimally useful indicators being IL-9, IL-5, IL-13 and IL-4. Equivalent, and minimal, Ag-dependent pro-inflammatory cytokine levels in both healthy and peanut allergic volunteers argues against a key role for such cytokines in maintenance of clinical tolerance to food antigens in humans.
format	article
author	Jungang Xie Larisa C Lotoski Rishma Chooniedass Ruey-Chyi Su F Estelle R Simons Joel Liem Allan B Becker Jude Uzonna Kent T HayGlass
author_facet	Jungang Xie Larisa C Lotoski Rishma Chooniedass Ruey-Chyi Su F Estelle R Simons Joel Liem Allan B Becker Jude Uzonna Kent T HayGlass
author_sort	Jungang Xie
title	Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.
title_short	Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.
title_full	Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.
title_fullStr	Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.
title_full_unstemmed	Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.
title_sort	elevated antigen-driven il-9 responses are prominent in peanut allergic humans.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/dc96061906fd4b90a42cd3dbd1da01ed
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Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans.

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