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A Mathematical Model for DC Vaccine Treatment of Type I Diabetes

Type I diabetes (T1D) is an autoimmune disease that can be managed, but for which there is currently no cure. Recent discoveries, particularly in mouse models, indicate that targeted modulation of the immune response has the potential to move an individual from a diabetic to a long-term, if not perm...

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Autores principales: Shtylla, Blerta, Gee, Marissa, Do, An, Shabahang, Shahrokh, Eldevik, Leif, de Pillis, Lisette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742690/
https://www.ncbi.nlm.nih.gov/pubmed/31555144
http://dx.doi.org/10.3389/fphys.2019.01107
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author Shtylla, Blerta
Gee, Marissa
Do, An
Shabahang, Shahrokh
Eldevik, Leif
de Pillis, Lisette
author_facet Shtylla, Blerta
Gee, Marissa
Do, An
Shabahang, Shahrokh
Eldevik, Leif
de Pillis, Lisette
author_sort Shtylla, Blerta
collection PubMed
description Type I diabetes (T1D) is an autoimmune disease that can be managed, but for which there is currently no cure. Recent discoveries, particularly in mouse models, indicate that targeted modulation of the immune response has the potential to move an individual from a diabetic to a long-term, if not permanent, healthy state. In this paper we develop a single compartment mathematical model that captures the dynamics of dendritic cells (DC and tDC), T cells (effector and regulatory), and macrophages in the development of type I diabetes. The model supports the hypothesis that differences in macrophage clearance rates play a significant role in determining whether or not an individual is likely to become diabetic subsequent to a significant immune challenge. With this model we are able to explore the effects of strengthening the anti-inflammatory component of the immune system in a vulnerable individual. Simulations indicate that there are windows of opportunity in which treatment intervention is more likely to be beneficial in protecting an individual from entering a diabetic state. This model framework can be used as a foundation for modeling future T1D treatments as they are developed.
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spelling pubmed-67426902019-09-25 A Mathematical Model for DC Vaccine Treatment of Type I Diabetes Shtylla, Blerta Gee, Marissa Do, An Shabahang, Shahrokh Eldevik, Leif de Pillis, Lisette Front Physiol Physiology Type I diabetes (T1D) is an autoimmune disease that can be managed, but for which there is currently no cure. Recent discoveries, particularly in mouse models, indicate that targeted modulation of the immune response has the potential to move an individual from a diabetic to a long-term, if not permanent, healthy state. In this paper we develop a single compartment mathematical model that captures the dynamics of dendritic cells (DC and tDC), T cells (effector and regulatory), and macrophages in the development of type I diabetes. The model supports the hypothesis that differences in macrophage clearance rates play a significant role in determining whether or not an individual is likely to become diabetic subsequent to a significant immune challenge. With this model we are able to explore the effects of strengthening the anti-inflammatory component of the immune system in a vulnerable individual. Simulations indicate that there are windows of opportunity in which treatment intervention is more likely to be beneficial in protecting an individual from entering a diabetic state. This model framework can be used as a foundation for modeling future T1D treatments as they are developed. Frontiers Media S.A. 2019-09-06 /pmc/articles/PMC6742690/ /pubmed/31555144 http://dx.doi.org/10.3389/fphys.2019.01107 Text en Copyright © 2019 Shtylla, Gee, Do, Shabahang, Eldevik and de Pillis. 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 Physiology
Shtylla, Blerta
Gee, Marissa
Do, An
Shabahang, Shahrokh
Eldevik, Leif
de Pillis, Lisette
A Mathematical Model for DC Vaccine Treatment of Type I Diabetes
title A Mathematical Model for DC Vaccine Treatment of Type I Diabetes
title_full A Mathematical Model for DC Vaccine Treatment of Type I Diabetes
title_fullStr A Mathematical Model for DC Vaccine Treatment of Type I Diabetes
title_full_unstemmed A Mathematical Model for DC Vaccine Treatment of Type I Diabetes
title_short A Mathematical Model for DC Vaccine Treatment of Type I Diabetes
title_sort mathematical model for dc vaccine treatment of type i diabetes
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742690/
https://www.ncbi.nlm.nih.gov/pubmed/31555144
http://dx.doi.org/10.3389/fphys.2019.01107
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