Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.

Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). D...

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Main Authors: Sara Anvari, Levi B Watkin, Charles G Minard, Kimberly Schuster, Oluwatomi Hassan, Aikaterini Anagnostou, Jordan S Orange, David B Corry, Carla M Davis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0264674
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author Sara Anvari
Levi B Watkin
Charles G Minard
Kimberly Schuster
Oluwatomi Hassan
Aikaterini Anagnostou
Jordan S Orange
David B Corry
Carla M Davis
author_facet Sara Anvari
Levi B Watkin
Charles G Minard
Kimberly Schuster
Oluwatomi Hassan
Aikaterini Anagnostou
Jordan S Orange
David B Corry
Carla M Davis
author_sort Sara Anvari
collection DOAJ
description Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5-12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. The distribution frequency of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) from peripheral blood samples were measured in vitro. A general linear mixed model was used, and included fixed effects for cohort (responder, non-responder, or healthy control), time (0-, 6-, 12-, 18-, and 24-weeks), and the cohort-time interaction term. P-values were adjusted for multiple hypothesis testing using Tukey's method. We observed that POIT responders had reduced TNFa producing myeloid dendritic cells (mDCs) compared to non-responders. Additionally, non-responders had increased OX40L expressing mDCs at 18-weeks compared to responders. In conclusion, our findings suggest that a reduced pro-inflammatory phenotype in DCs could potentially serve as a predictor of early outcome and success of POIT desensitization.
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spelling doaj.art-f72371d7158a42e3ae27743a67665d162023-07-27T05:31:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175e026467410.1371/journal.pone.0264674Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.Sara AnvariLevi B WatkinCharles G MinardKimberly SchusterOluwatomi HassanAikaterini AnagnostouJordan S OrangeDavid B CorryCarla M DavisDendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5-12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. The distribution frequency of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) from peripheral blood samples were measured in vitro. A general linear mixed model was used, and included fixed effects for cohort (responder, non-responder, or healthy control), time (0-, 6-, 12-, 18-, and 24-weeks), and the cohort-time interaction term. P-values were adjusted for multiple hypothesis testing using Tukey's method. We observed that POIT responders had reduced TNFa producing myeloid dendritic cells (mDCs) compared to non-responders. Additionally, non-responders had increased OX40L expressing mDCs at 18-weeks compared to responders. In conclusion, our findings suggest that a reduced pro-inflammatory phenotype in DCs could potentially serve as a predictor of early outcome and success of POIT desensitization.https://doi.org/10.1371/journal.pone.0264674
spellingShingle Sara Anvari
Levi B Watkin
Charles G Minard
Kimberly Schuster
Oluwatomi Hassan
Aikaterini Anagnostou
Jordan S Orange
David B Corry
Carla M Davis
Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.
PLoS ONE
title Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.
title_full Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.
title_fullStr Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.
title_full_unstemmed Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.
title_short Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy.
title_sort reduced pro inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy
url https://doi.org/10.1371/journal.pone.0264674
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