Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus

Liguang Sun, Robert Brown, Shande Chen, Qichuan Zhuge, Dong Ming Su

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Age-related decline in the generation of T cells is associated with two primary lymphoid organs, the bone marrow (BM) and thymus. Both organs contain lympho-hematopoietic progenitor/stem cells (LPCs) and non-hematopoietic stromal/niche cells. Murine model showed this decline is not due to reduced quantities of LPCs, nor autonomous defects in LPCs, but rather defects in their niche cells. However, this viewpoint is challenged by the fact that aged BM progenitors have a myeloid skew. By grafting young wild-type (WT) BM progenitors into aged IL-7R-/-hosts, which possess WTequivalent niches although LPCs are defect, we demonstrated that these young BM progenitors also exhibited a myeloid skew. We, further, demonstrated that aged BM progenitors, recruited by a grafted fetal thymus in the in vivo microenvironment, were able to compete with their young counterparts, although the in vitro manipulated old BM cells were not able to do so in conventional BM transplantation. Both LPCs and their niche cells inevitably get old with increasing organismal age, but aging in niche cells occurred much earlier than in LPCs by an observation in thymic Tlymphopoiesis. Therefore, the aging induced decline in competence to generate T cells is primarily dependent on status of the progenitor niche cells in the BM and thymus.

Original languageEnglish
Pages (from-to)606-619
Number of pages14
JournalAging
Volume4
Issue number9
DOIs
StatePublished - 2012

Keywords

  • Aging
  • Bone marrow
  • Competitive repopulation
  • Hematopoiesis
  • Microenvironment
  • Niche cells
  • T-lineage cells
  • Thymic stromal cells

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