Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis

The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involv...

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Main Authors: Fatemeh Shirafkan, Luca Hensel, Kristin Rattay
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1339714/full
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author Fatemeh Shirafkan
Luca Hensel
Kristin Rattay
author_facet Fatemeh Shirafkan
Luca Hensel
Kristin Rattay
author_sort Fatemeh Shirafkan
collection DOAJ
description The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involves the elimination of self-reactive T cells, a mechanism essential for averting autoimmunity. Disruption of the thymic T cell selection mechanisms can lead to the development of autoimmune diseases. In the dynamic microenvironment of the thymus, T cell migration and interactions with thymic stromal cells are critical for the selection processes that ensure self-tolerance. Thymic epithelial cells are particularly significant in this context, presenting self-antigens and inducing the negative selection of autoreactive T cells. Further, the synergistic roles of thymic fibroblasts, B cells, and dendritic cells in antigen presentation, selection and the development of regulatory T cells are pivotal in maintaining immune responses tightly regulated. This review article collates these insights, offering a comprehensive examination of the multifaceted role of thymic tissue homeostasis in the establishment of immune tolerance and its implications in the prevention of autoimmune diseases. Additionally, the developmental pathways of the thymus are explored, highlighting how genetic aberrations can disrupt thymic architecture and function, leading to autoimmune conditions. The impact of infections on immune tolerance is another critical area, with pathogens potentially triggering autoimmunity by altering thymic homeostasis. Overall, this review underscores the integral role of thymic tissue homeostasis in the prevention of autoimmune diseases, discussing insights into potential therapeutic strategies and examining putative avenues for future research on developing thymic-based therapies in treating and preventing autoimmune conditions.
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spelling doaj.art-b9045abc53e54bb399a2470a4fad68e62024-03-20T05:14:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13397141339714Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasisFatemeh ShirafkanLuca HenselKristin RattayThe intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involves the elimination of self-reactive T cells, a mechanism essential for averting autoimmunity. Disruption of the thymic T cell selection mechanisms can lead to the development of autoimmune diseases. In the dynamic microenvironment of the thymus, T cell migration and interactions with thymic stromal cells are critical for the selection processes that ensure self-tolerance. Thymic epithelial cells are particularly significant in this context, presenting self-antigens and inducing the negative selection of autoreactive T cells. Further, the synergistic roles of thymic fibroblasts, B cells, and dendritic cells in antigen presentation, selection and the development of regulatory T cells are pivotal in maintaining immune responses tightly regulated. This review article collates these insights, offering a comprehensive examination of the multifaceted role of thymic tissue homeostasis in the establishment of immune tolerance and its implications in the prevention of autoimmune diseases. Additionally, the developmental pathways of the thymus are explored, highlighting how genetic aberrations can disrupt thymic architecture and function, leading to autoimmune conditions. The impact of infections on immune tolerance is another critical area, with pathogens potentially triggering autoimmunity by altering thymic homeostasis. Overall, this review underscores the integral role of thymic tissue homeostasis in the prevention of autoimmune diseases, discussing insights into potential therapeutic strategies and examining putative avenues for future research on developing thymic-based therapies in treating and preventing autoimmune conditions.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1339714/fullthymusautoimmune diseasetolerancetissue homeostasismTECthymocytes
spellingShingle Fatemeh Shirafkan
Luca Hensel
Kristin Rattay
Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
Frontiers in Immunology
thymus
autoimmune disease
tolerance
tissue homeostasis
mTEC
thymocytes
title Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
title_full Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
title_fullStr Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
title_full_unstemmed Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
title_short Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
title_sort immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
topic thymus
autoimmune disease
tolerance
tissue homeostasis
mTEC
thymocytes
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1339714/full
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AT lucahensel immunetoleranceandthepreventionofautoimmunediseasesessentiallydependonthymictissuehomeostasis
AT kristinrattay immunetoleranceandthepreventionofautoimmunediseasesessentiallydependonthymictissuehomeostasis