Kreins, AY;
Bonfanti, P;
Davies, EG;
(2021)
Current and Future Therapeutic Approaches for Thymic Stromal Cell Defects.
Frontiers in Immunology
, 12
, Article 655354. 10.3389/fimmu.2021.655354.
Preview |
Text
fimmu-12-655354.pdf - Published Version Download (684kB) | Preview |
Abstract
Inborn errors of thymic stromal cell development and function lead to impaired T-cell development resulting in a susceptibility to opportunistic infections and autoimmunity. In their most severe form, congenital athymia, these disorders are life-threatening if left untreated. Athymia is rare and is typically associated with complete DiGeorge syndrome, which has multiple genetic and environmental etiologies. It is also found in rare cases of T-cell lymphopenia due to Nude SCID and Otofaciocervical Syndrome type 2, or in the context of genetically undefined defects. This group of disorders cannot be corrected by hematopoietic stem cell transplantation, but upon timely recognition as thymic defects, can successfully be treated by thymus transplantation using cultured postnatal thymic tissue with the generation of naïve T-cells showing a diverse repertoire. Mortality after this treatment usually occurs before immune reconstitution and is mainly associated with infections most often acquired pre-transplantation. In this review, we will discuss the current approaches to the diagnosis and management of thymic stromal cell defects, in particular those resulting in athymia. We will discuss the impact of the expanding implementation of newborn screening for T-cell lymphopenia, in combination with next generation sequencing, as well as the role of novel diagnostic tools distinguishing between hematopoietic and thymic stromal cell defects in facilitating the early consideration for thymus transplantation of an increasing number of patients and disorders. Immune reconstitution after the current treatment is usually incomplete with relatively common inflammatory and autoimmune complications, emphasizing the importance for improving strategies for thymus replacement therapy by optimizing the current use of postnatal thymus tissue and developing new approaches using engineered thymus tissue.
| Type: | Article |
|---|---|
| Title: | Current and Future Therapeutic Approaches for Thymic Stromal Cell Defects |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2021.655354 |
| Publisher version: | http://dx.doi.org/10.3389/fimmu.2021.655354 |
| Language: | English |
| Additional information: | © 2021 Kreins, Bonfanti and Davies. 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) and the copyright owner(s) 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. |
| Keywords: | DiGeorge syndrome, FOXN1, PAX1, primary immunodeficiency, regenerative medicine, severe combined immunodeficiency (SCID), thymus transplantation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126066 |
Archive Staff Only
 |
View Item |
