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<p>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<sup>+</sup> 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<sup>+</sup> 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.</p>

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Mesenchymal thymic niche cells enable regeneration of the adult thymus and T cell immunity

  • 期刊论文

  • 发表日期：

    2025年10月30日

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  • Karin Gustafsson,
  • Sergey Isaev,
  • Kamdin Mirsanaye,
  • Johanna Hofmann,
  • Kameron A. Kooshesh,
  • Ninib Baryawno,
  • Anna Kiem,
  • Nicolas Severe,
  • Ting Zhao,
  • Elizabeth W. Scadden,
  • Joel A. Spencer,
  • Christian Burns,
  • Kumaran Akilan,
  • Nikolaos Barkas,
  • Hayalneh Gessessew,
  • Konstantinos D. Kokkaliaris,
  • Charles P. Lin,
  • Peter V. Kharchenko,
  • David T. Scadden

摘要

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.