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Rag Defects and Thymic Stroma: Lessons from Animal Models
Thymocytes and thymic epithelial cells (TECs) cross-talk is essential to support T cell development and preserve thymic architecture and maturation of TECs and Foxp3(+) natural regulatory T cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic me...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114104/ https://www.ncbi.nlm.nih.gov/pubmed/25076946 http://dx.doi.org/10.3389/fimmu.2014.00259 |
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author | Marrella, Veronica Poliani, Pietro Luigi Notarangelo, Luigi Daniele Grassi, Fabio Villa, Anna |
author_facet | Marrella, Veronica Poliani, Pietro Luigi Notarangelo, Luigi Daniele Grassi, Fabio Villa, Anna |
author_sort | Marrella, Veronica |
collection | PubMed |
description | Thymocytes and thymic epithelial cells (TECs) cross-talk is essential to support T cell development and preserve thymic architecture and maturation of TECs and Foxp3(+) natural regulatory T cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development [leading to severe combined immune deficiency (SCID)] or late stages in thymocyte maturation (resulting in combined immunodeficiency). Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS). In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signaling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution. |
format | Online Article Text |
id | pubmed-4114104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-41141042014-07-30 Rag Defects and Thymic Stroma: Lessons from Animal Models Marrella, Veronica Poliani, Pietro Luigi Notarangelo, Luigi Daniele Grassi, Fabio Villa, Anna Front Immunol Immunology Thymocytes and thymic epithelial cells (TECs) cross-talk is essential to support T cell development and preserve thymic architecture and maturation of TECs and Foxp3(+) natural regulatory T cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development [leading to severe combined immune deficiency (SCID)] or late stages in thymocyte maturation (resulting in combined immunodeficiency). Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS). In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signaling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution. Frontiers Media S.A. 2014-06-02 /pmc/articles/PMC4114104/ /pubmed/25076946 http://dx.doi.org/10.3389/fimmu.2014.00259 Text en Copyright © 2014 Marrella, Poliani, Notarangelo, Grassi and Villa. http://creativecommons.org/licenses/by/3.0/ 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) or licensor 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 Marrella, Veronica Poliani, Pietro Luigi Notarangelo, Luigi Daniele Grassi, Fabio Villa, Anna Rag Defects and Thymic Stroma: Lessons from Animal Models |
title | Rag Defects and Thymic Stroma: Lessons from Animal Models |
title_full | Rag Defects and Thymic Stroma: Lessons from Animal Models |
title_fullStr | Rag Defects and Thymic Stroma: Lessons from Animal Models |
title_full_unstemmed | Rag Defects and Thymic Stroma: Lessons from Animal Models |
title_short | Rag Defects and Thymic Stroma: Lessons from Animal Models |
title_sort | rag defects and thymic stroma: lessons from animal models |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114104/ https://www.ncbi.nlm.nih.gov/pubmed/25076946 http://dx.doi.org/10.3389/fimmu.2014.00259 |
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