Bone Marrow Mesenchymal Stem and Progenitor Cells Induce Monocyte Emigration in Response to Circulating Toll-like Receptor Ligands

Chao Shi, Ting Jia, Simon Mendez-Ferrer, Tobias M. Hohl, Natalya V. Serbina, Lauren Lipuma, Ingrid Leiner, Ming O. Li, Paul S. Frenette, Eric G. Pamer

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277 Scopus citations

Abstract

Inflammatory (Ly6Chi CCR2+) monocytes provide defense against infections but also contribute to autoimmune diseases and atherosclerosis. Monocytes originate from bone marrow and their entry into the bloodstream requires stimulation of CCR2 chemokine receptor by monocyte chemotactic protein-1 (MCP1). How monocyte emigration from bone marrow is triggered by remote infections remains unclear. We demonstrated that low concentrations of Toll-like receptor (TLR) ligands in the bloodstream drive CCR2-dependent emigration of monocytes from bone marrow. Bone marrow mesenchymal stem cells (MSCs) and their progeny, including CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells, rapidly expressed MCP1 in response to circulating TLR ligands or bacterial infection and induced monocyte trafficking into the bloodstream. Targeted deletion of MCP1 from MSCs impaired monocyte emigration from bone marrow. Our findings suggest that bone marrow MSCs and CAR cells respond to circulating microbial molecules and regulate bloodstream monocyte frequencies by secreting MCP1 in proximity to bone marrow vascular sinuses.

Original languageEnglish (US)
Pages (from-to)590-601
Number of pages12
JournalImmunity
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 22 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Shi, C., Jia, T., Mendez-Ferrer, S., Hohl, T. M., Serbina, N. V., Lipuma, L., ... Pamer, E. G. (2011). Bone Marrow Mesenchymal Stem and Progenitor Cells Induce Monocyte Emigration in Response to Circulating Toll-like Receptor Ligands. Immunity, 34(4), 590-601. https://doi.org/10.1016/j.immuni.2011.02.016