淋巴细胞生成
生物
T细胞
细胞生物学
免疫系统
间充质干细胞
免疫学
干细胞
祖细胞
CCL19型
间质细胞
趋化因子
癌症研究
趋化因子受体
作者
Karin Gustafsson,Sergey Isaev,Kameron Kooshesh,Ninib Baryawno,Konstantinos D. Kokkaliaris,Nicolas Sévère,Ting Zhao,Elizabeth W. Scadden,Joel A. Spencer,Christian Burns,Kumaran Akilan,Nikolaos Barkas,Hayalneh Gessessew,Charles P. Lin,Peter V. Kharchenko,David T. Scadden
标识
DOI:10.1101/2022.10.12.511184
摘要
Abstract Thymic atrophy and the progressive immune decline that accompanies it is a major health problem, chronically with age and acutely with immune injury. No solution has been defined. 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 located perivascularly in the cortical-medullary junction, medulla and subcapsular regions. Cell depletion demonstrated that it recruits T competent cells to the thymus and initiates T lymphopoiesis in vivo . This subset distinctively expresses the chemokine Ccl19 necessary for niche functions. It markedly declines with age and in the acute setting of hematopoietic stem cell transplant conditioning. When isolated and adoptively transferred, these cells durably engrafted the atrophic thymus, recruited early T progenitors, increased T cell neogenesis, expanded TCR complexity and enhanced T cell response to vaccination. These data define a thymus lymphopoietic niche cell type that may be manipulated therapeutically to regenerate T lymphopoiesis.
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