TY  - JOUR
AU  - Gustafsson, Karin
AU  - Isaev, Sergey
AU  - Mirsanaye, Kamdin
AU  - Hofmann, Johanna
AU  - Kooshesh, Kameron A
AU  - Baryawno, Ninib
AU  - Kiem, Anna
AU  - Severe, Nicolas
AU  - Zhao, Ting
AU  - Scadden, Elizabeth W
AU  - Spencer, Joel A
AU  - Burns, Christian
AU  - Akilan, Kumaran
AU  - Barkas, Nikolaos
AU  - Gessessew, Hayalneh
AU  - Kokkaliaris, Konstantinos
AU  - Lin, Charles P
AU  - Kharchenko, Peter V
AU  - Scadden, David T
TI  - Mesenchymal thymic niche cells enable regeneration of the adult thymus and T cell immunity.
JO  - Nature biotechnology
VL  - nn
SN  - 1087-0156
CY  - New York, NY
PB  - Springer Nature
M1  - DKFZ-2025-02260
SP  - nn
PY  - 2025
N1  - epub
AB  - Thymic atrophy and the progressive immune decline that accompanies it is a major health problem, chronically with age and acutely with immune injury. No definitive solution is available. Here we demonstrate that one of the three mesenchymal cell subsets identified by single-cell analysis of human and mouse thymic stroma is a critical niche component for T lymphopoiesis. The Postn+ subset is perivascular, and its depletion abrogates T cell progenitor recruitment, likely through production of the chemokine Ccl19. It markedly declines with age and in the acute setting of hematopoietic stem cell transplant conditioning. When isolated and adoptively transferred, Postn+ cells durably engraft the atrophic thymus, recruit early T progenitors, increase T cell neogenesis and enhance T cell response to vaccination. More readily available mesenchymal populations expressing Ccl19 provide similar effects. These data define a thymus lymphopoietic niche cell type that may be manipulated therapeutically to regenerate T lymphopoiesis.
LB  - PUB:(DE-HGF)16
C6  - pmid:41168496
DO  - DOI:10.1038/s41587-025-02864-w
UR  - https://inrepo02.dkfz.de/record/305610
ER  -