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.

Human FOXN1-deficiency is associated with ab double-negative and FoxP3+ T-cell expansions that are distinctly moludated upon thymic transplantation / Albuquerque, A. S.; Marques, J. G.; Silvia, S. L.; Ligeiro, D.; Devlin, B. H.; Dutrieux, J.; Cheynier, R.; Pignata, Claudio; Victorino, R. M. M.; Market, M. L.; Sousa, A. E.. - In: PLOS ONE. - ISSN 1932-6203. - 7:(2012), pp. e37042-e37042. [10.1371/journal.pone.0037042]

Human FOXN1-deficiency is associated with ab double-negative and FoxP3+ T-cell expansions that are distinctly moludated upon thymic transplantation.

PIGNATA, CLAUDIO;
2012

Abstract

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.
2012
Human FOXN1-deficiency is associated with ab double-negative and FoxP3+ T-cell expansions that are distinctly moludated upon thymic transplantation / Albuquerque, A. S.; Marques, J. G.; Silvia, S. L.; Ligeiro, D.; Devlin, B. H.; Dutrieux, J.; Cheynier, R.; Pignata, Claudio; Victorino, R. M. M.; Market, M. L.; Sousa, A. E.. - In: PLOS ONE. - ISSN 1932-6203. - 7:(2012), pp. e37042-e37042. [10.1371/journal.pone.0037042]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/461203
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