Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation.
Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T...
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2012
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oai:doaj.org-article:9f3b322d36ec49c49ade3fd6d5172c7d2021-11-18T07:19:08ZHuman FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation.1932-620310.1371/journal.pone.0037042https://doaj.org/article/9f3b322d36ec49c49ade3fd6d5172c7d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22590644/?tool=EBIhttps://doaj.org/toc/1932-6203Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.Adriana S AlbuquerqueJosé G MarquesSusana L SilvaDario LigeiroBlythe H DevlinJacques DutrieuxRémi CheynierClaudio PignataRui M M VictorinoM Louise MarkertAna E SousaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37042 (2012) |
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Medicine R Science Q Adriana S Albuquerque José G Marques Susana L Silva Dario Ligeiro Blythe H Devlin Jacques Dutrieux Rémi Cheynier Claudio Pignata Rui M M Victorino M Louise Markert Ana E Sousa Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation. |
| description |
Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings. |
| format |
article |
| author |
Adriana S Albuquerque José G Marques Susana L Silva Dario Ligeiro Blythe H Devlin Jacques Dutrieux Rémi Cheynier Claudio Pignata Rui M M Victorino M Louise Markert Ana E Sousa |
| author_facet |
Adriana S Albuquerque José G Marques Susana L Silva Dario Ligeiro Blythe H Devlin Jacques Dutrieux Rémi Cheynier Claudio Pignata Rui M M Victorino M Louise Markert Ana E Sousa |
| author_sort |
Adriana S Albuquerque |
| title |
Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation. |
| title_short |
Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation. |
| title_full |
Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation. |
| title_fullStr |
Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation. |
| title_full_unstemmed |
Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation. |
| title_sort |
human foxn1-deficiency is associated with αβ double-negative and foxp3+ t-cell expansions that are distinctly modulated upon thymic transplantation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/9f3b322d36ec49c49ade3fd6d5172c7d |
| work_keys_str_mv |
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