Cargando…
FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program
T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs) drive T cell differentiation, educa...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709140/ https://www.ncbi.nlm.nih.gov/pubmed/23874334 http://dx.doi.org/10.3389/fimmu.2013.00187 |
_version_ | 1782276713521086464 |
---|---|
author | Romano, Rosa Palamaro, Loredana Fusco, Anna Giardino, Giuliana Gallo, Vera Del Vecchio, Luigi Pignata, Claudio |
author_facet | Romano, Rosa Palamaro, Loredana Fusco, Anna Giardino, Giuliana Gallo, Vera Del Vecchio, Luigi Pignata, Claudio |
author_sort | Romano, Rosa |
collection | PubMed |
description | T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs) drive T cell differentiation, education, and selection processes, while the thymocyte-dependent signals allow thymic epithelial cells (TECs) to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1, and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1) gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the post-natal thymus. An inborn null mutation in FOXN1 leads to Nude/severe combined immunodeficiency (SCID) phenotype in mouse, rat, and humans. In Foxn1(−/−) nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy, and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality. |
format | Online Article Text |
id | pubmed-3709140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37091402013-07-19 FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program Romano, Rosa Palamaro, Loredana Fusco, Anna Giardino, Giuliana Gallo, Vera Del Vecchio, Luigi Pignata, Claudio Front Immunol Immunology T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs) drive T cell differentiation, education, and selection processes, while the thymocyte-dependent signals allow thymic epithelial cells (TECs) to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1, and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1) gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the post-natal thymus. An inborn null mutation in FOXN1 leads to Nude/severe combined immunodeficiency (SCID) phenotype in mouse, rat, and humans. In Foxn1(−/−) nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy, and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality. Frontiers Media S.A. 2013-07-12 /pmc/articles/PMC3709140/ /pubmed/23874334 http://dx.doi.org/10.3389/fimmu.2013.00187 Text en Copyright © 2013 Romano, Palamaro, Fusco, Giardino, Gallo, Del Vecchio and Pignata. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Immunology Romano, Rosa Palamaro, Loredana Fusco, Anna Giardino, Giuliana Gallo, Vera Del Vecchio, Luigi Pignata, Claudio FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program |
title | FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program |
title_full | FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program |
title_fullStr | FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program |
title_full_unstemmed | FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program |
title_short | FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program |
title_sort | foxn1: a master regulator gene of thymic epithelial development program |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709140/ https://www.ncbi.nlm.nih.gov/pubmed/23874334 http://dx.doi.org/10.3389/fimmu.2013.00187 |
work_keys_str_mv | AT romanorosa foxn1amasterregulatorgeneofthymicepithelialdevelopmentprogram AT palamaroloredana foxn1amasterregulatorgeneofthymicepithelialdevelopmentprogram AT fuscoanna foxn1amasterregulatorgeneofthymicepithelialdevelopmentprogram AT giardinogiuliana foxn1amasterregulatorgeneofthymicepithelialdevelopmentprogram AT gallovera foxn1amasterregulatorgeneofthymicepithelialdevelopmentprogram AT delvecchioluigi foxn1amasterregulatorgeneofthymicepithelialdevelopmentprogram AT pignataclaudio foxn1amasterregulatorgeneofthymicepithelialdevelopmentprogram |