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Mutant mice treated with tamoxifen showed total or near-total regeneration of their youthful thymus, while control mice also given tamoxifen showed predictable thymus function for their age. This held true for both the size of the organ itself and the abundance of the T-cells it produces. The regeneration seems to arise from the fact that FOXN1 is a transcription factor that controls expression of several other genes, and that these genes activate stem cell-like action in some thymus cells. By restoring FOXN1 levels, the researchers seem to have convinced the thymus to de-age itself — at least, in this one very specific way.
The researchers are quick to point out the possible benefits to elderly people, or those afflicted by immune diseases. Increasing the ability to fight infection could also revolutionize hospital medicine, helping vulnerable patients fight infection by “overclocking” the thymus to produce a boost of white blood cells. Restoring the immune response of sick and elderly people would be, without an ounce of hyperbole, one of the most important medical advances in all of human history.
Regeneration of the aged thymus by a single transcription factor
Thymic involution is central to the decline in immune system function that occurs with age. By regenerating the thymus, it may therefore be possible to improve the ability of the aged immune system to respond to novel antigens. Recently, diminished expression of the thymic epithelial cell (TEC)-specific transcription factor Forkhead box N1 (FOXN1) has been implicated as a component of the mechanism regulating age-related involution. The effects of upregulating FOXN1 function in the aged thymus are, however, unknown. Here, we show that forced, TEC-specific upregulation of FOXN1 in the fully involuted thymus of aged mice results in robust thymus regeneration characterized by increased thymopoiesis and increased naive T cell output. We demonstrate that the regenerated organ closely resembles the juvenile thymus in terms of architecture and gene expression profile, and further show that this FOXN1-mediated regeneration stems from an enlarged TEC compartment, rebuilt from progenitor TECs. Collectively, our data establish that upregulation of a single transcription factor can substantially reverse age-related thymic involution, identifying FOXN1 as a specific target for improving thymus function and, thus, immune competence in patients. More widely, they demonstrate that organ regeneration in an aged mammal can be directed by manipulation of a single transcription factor, providing a provocative paradigm that may be of broad impact for regenerative biology
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Reposted via Next Big Future
Mutant mice treated with tamoxifen showed total or near-total regeneration of their youthful thymus, while control mice also given tamoxifen showed predictable thymus function for their age. This held true for both the size of the organ itself and the abundance of the T-cells it produces. The regeneration seems to arise from the fact that FOXN1 is a transcription factor that controls expression of several other genes, and that these genes activate stem cell-like action in some thymus cells. By restoring FOXN1 levels, the researchers seem to have convinced the thymus to de-age itself — at least, in this one very specific way.
The researchers are quick to point out the possible benefits to elderly people, or those afflicted by immune diseases. Increasing the ability to fight infection could also revolutionize hospital medicine, helping vulnerable patients fight infection by “overclocking” the thymus to produce a boost of white blood cells. Restoring the immune response of sick and elderly people would be, without an ounce of hyperbole, one of the most important medical advances in all of human history.
Regeneration of the aged thymus by a single transcription factor
Thymic involution is central to the decline in immune system function that occurs with age. By regenerating the thymus, it may therefore be possible to improve the ability of the aged immune system to respond to novel antigens. Recently, diminished expression of the thymic epithelial cell (TEC)-specific transcription factor Forkhead box N1 (FOXN1) has been implicated as a component of the mechanism regulating age-related involution. The effects of upregulating FOXN1 function in the aged thymus are, however, unknown. Here, we show that forced, TEC-specific upregulation of FOXN1 in the fully involuted thymus of aged mice results in robust thymus regeneration characterized by increased thymopoiesis and increased naive T cell output. We demonstrate that the regenerated organ closely resembles the juvenile thymus in terms of architecture and gene expression profile, and further show that this FOXN1-mediated regeneration stems from an enlarged TEC compartment, rebuilt from progenitor TECs. Collectively, our data establish that upregulation of a single transcription factor can substantially reverse age-related thymic involution, identifying FOXN1 as a specific target for improving thymus function and, thus, immune competence in patients. More widely, they demonstrate that organ regeneration in an aged mammal can be directed by manipulation of a single transcription factor, providing a provocative paradigm that may be of broad impact for regenerative biology
Read more »
Reposted via Next Big Future
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