The role of thymic tolerance in CNS autoimmune disease

The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms...

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Main Authors: Handel, A, Irani, S, Holländer, G
Format: Journal article
Published: Springer Nature 2018
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author Handel, A
Irani, S
Holländer, G
author_facet Handel, A
Irani, S
Holländer, G
author_sort Handel, A
collection OXFORD
description The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with an overt autoreactive specificity are eliminated before they emigrate to the periphery and control the generation of thymic regulatory T cells. Evidence from animal studies demonstrates that thymic T cell selection is important for establishing tolerance to autoantigens. However, there is a considerable knowledge gap regarding the role of thymic selection in autoimmune conditions of the human CNS. In this Review, we critically examine the current body of experimental evidence for the contribution of thymic tolerance to CNS autoimmune diseases. An understanding of why dysfunction of either thymic or peripheral tolerance mechanisms rarely leads to CNS inflammation is currently lacking. We examine the potential of de novo T cell formation and thymic selection as novel therapeutic avenues and highlight areas for future study that are likely to make these targets the focus of future treatments.
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spelling oxford-uuid:47041b1f-d626-4caa-abd7-2ab61703b7322022-03-26T15:17:27ZThe role of thymic tolerance in CNS autoimmune diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:47041b1f-d626-4caa-abd7-2ab61703b732Symplectic Elements at OxfordSpringer Nature2018Handel, AIrani, SHolländer, GThe contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with an overt autoreactive specificity are eliminated before they emigrate to the periphery and control the generation of thymic regulatory T cells. Evidence from animal studies demonstrates that thymic T cell selection is important for establishing tolerance to autoantigens. However, there is a considerable knowledge gap regarding the role of thymic selection in autoimmune conditions of the human CNS. In this Review, we critically examine the current body of experimental evidence for the contribution of thymic tolerance to CNS autoimmune diseases. An understanding of why dysfunction of either thymic or peripheral tolerance mechanisms rarely leads to CNS inflammation is currently lacking. We examine the potential of de novo T cell formation and thymic selection as novel therapeutic avenues and highlight areas for future study that are likely to make these targets the focus of future treatments.
spellingShingle Handel, A
Irani, S
Holländer, G
The role of thymic tolerance in CNS autoimmune disease
title The role of thymic tolerance in CNS autoimmune disease
title_full The role of thymic tolerance in CNS autoimmune disease
title_fullStr The role of thymic tolerance in CNS autoimmune disease
title_full_unstemmed The role of thymic tolerance in CNS autoimmune disease
title_short The role of thymic tolerance in CNS autoimmune disease
title_sort role of thymic tolerance in cns autoimmune disease
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