Nkx2-5(+)islet1(+) mesenchymal precursors generate distinct spleen stromal cell subsets and participate in restoring stromal network integrity

Immunity. 2013 Apr 18;38(4):782-91. doi: 10.1016/j.immuni.2012.12.005.

Abstract

Secondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5(+)Islet1(+) lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Dendritic Cells, Follicular / metabolism*
  • Dendritic Cells, Follicular / pathology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / metabolism*
  • LIM-Homeodomain Proteins / metabolism*
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / physiopathology
  • Lymphocytic choriomeningitis virus / physiology*
  • Mesenchymal Stem Cells / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Regeneration
  • Spleen / pathology*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transcription Factors / metabolism*

Substances

  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Nkx2-5 protein, mouse
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1