Fight Aging!

You may recall that researchers have shown that endothelial progenitor cells can restore function to an atrophied thymus. Here, researchers identify a particular subset of functional cells in the thymus that can achieve the same result. The thymus loses active tissue with age, and this loss is a major contribution to the age-related decline of the immune system. The thymus is where thymocytes, created in the bone marrow, mature into new T cells of the adaptive immune system. Absent this supply of T cell reinforcements, the immune system becomes ever more crowded, year after year, with dysfunctional, broken cells. Restoring the aged thymus to enable production of T cells one more is an important goal for the rejuvenation research community.

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 this cell population 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 T cell receptor 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.

Link: https://doi.org/10.1101/2022.10.12.511184