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Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes

Type-1 Diabetes (T1D) is a complex polygenic autoimmune disorder involving T-cell driven beta-cell destruction leading to hyperglycemia. There is no cure for T1D and patients rely on exogenous insulin administration for disease management. T1D is associated with specific disease susceptible alleles....

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Autores principales: Majumdar, Shubhabrata, Lin, Yong, Bettini, Matthew L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434376/
https://www.ncbi.nlm.nih.gov/pubmed/36059452
http://dx.doi.org/10.3389/fimmu.2022.974178
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author Majumdar, Shubhabrata
Lin, Yong
Bettini, Matthew L.
author_facet Majumdar, Shubhabrata
Lin, Yong
Bettini, Matthew L.
author_sort Majumdar, Shubhabrata
collection PubMed
description Type-1 Diabetes (T1D) is a complex polygenic autoimmune disorder involving T-cell driven beta-cell destruction leading to hyperglycemia. There is no cure for T1D and patients rely on exogenous insulin administration for disease management. T1D is associated with specific disease susceptible alleles. However, the predisposition to disease development is not solely predicted by them. This is best exemplified by the observation that a monozygotic twin has just a 35% chance of developing T1D after their twin’s diagnosis. This makes a strong case for environmental triggers playing an important role in T1D incidence. Multiple studies indicate that commensal gut microbiota and environmental factors that alter their composition might exacerbate or protect against T1D onset. In this review, we discuss recent literature highlighting microbial species associated with T1D. We explore mechanistic studies which propose how some of these microbial species can modulate adaptive immune responses in T1D, with an emphasis on T-cell responses. We cover topics ranging from gut-thymus and gut-pancreas communication, microbial regulation of peripheral tolerance, to molecular mimicry of islet antigens by microbial peptides. In light of the accumulating evidence on commensal influences in neonatal thymocyte development, we also speculate on the link between molecular mimicry and thymic selection in the context of T1D pathogenesis. Finally, we explore how these observations could inform future therapeutic approaches in this disease.
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spelling pubmed-94343762022-09-02 Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes Majumdar, Shubhabrata Lin, Yong Bettini, Matthew L. Front Immunol Immunology Type-1 Diabetes (T1D) is a complex polygenic autoimmune disorder involving T-cell driven beta-cell destruction leading to hyperglycemia. There is no cure for T1D and patients rely on exogenous insulin administration for disease management. T1D is associated with specific disease susceptible alleles. However, the predisposition to disease development is not solely predicted by them. This is best exemplified by the observation that a monozygotic twin has just a 35% chance of developing T1D after their twin’s diagnosis. This makes a strong case for environmental triggers playing an important role in T1D incidence. Multiple studies indicate that commensal gut microbiota and environmental factors that alter their composition might exacerbate or protect against T1D onset. In this review, we discuss recent literature highlighting microbial species associated with T1D. We explore mechanistic studies which propose how some of these microbial species can modulate adaptive immune responses in T1D, with an emphasis on T-cell responses. We cover topics ranging from gut-thymus and gut-pancreas communication, microbial regulation of peripheral tolerance, to molecular mimicry of islet antigens by microbial peptides. In light of the accumulating evidence on commensal influences in neonatal thymocyte development, we also speculate on the link between molecular mimicry and thymic selection in the context of T1D pathogenesis. Finally, we explore how these observations could inform future therapeutic approaches in this disease. Frontiers Media S.A. 2022-08-18 /pmc/articles/PMC9434376/ /pubmed/36059452 http://dx.doi.org/10.3389/fimmu.2022.974178 Text en Copyright © 2022 Majumdar, Lin and Bettini https://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
Majumdar, Shubhabrata
Lin, Yong
Bettini, Matthew L.
Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes
title Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes
title_full Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes
title_fullStr Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes
title_full_unstemmed Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes
title_short Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes
title_sort host-microbiota interactions shaping t-cell response and tolerance in type 1 diabetes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434376/
https://www.ncbi.nlm.nih.gov/pubmed/36059452
http://dx.doi.org/10.3389/fimmu.2022.974178
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