Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency

Immunity. 2016 Jun 21;44(6):1434-43. doi: 10.1016/j.immuni.2016.05.012. Epub 2016 Jun 14.


Sepsis is a host inflammatory response to severe infection associated with high mortality that is caused by lymphopenia-associated immunodeficiency. However, it is unknown how lymphopenia persists after the accelerated lymphocyte apoptosis subsides. Here we show that sepsis rapidly ablated osteoblasts, which reduced the number of common lymphoid progenitors (CLPs). Osteoblast ablation or inducible deletion of interleukin-7 (IL-7) in osteoblasts recapitulated the lymphopenic phenotype together with a lower CLP number without affecting hematopoietic stem cells (HSCs). Pharmacological activation of osteoblasts improved sepsis-induced lymphopenia. This study demonstrates a reciprocal interaction between the immune and bone systems, in which acute inflammation induces a defect in bone cells resulting in lymphopenia-associated immunodeficiency, indicating that bone cells comprise a therapeutic target in certain life-threatening immune reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Immunologic Deficiency Syndromes / immunology*
  • Interleukin-7 / genetics
  • Interleukin-7 / metabolism*
  • Lymphocyte Depletion
  • Lymphoid Progenitor Cells / physiology*
  • Lymphopenia
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoblasts / physiology*
  • Sepsis / immunology*
  • T-Lymphocytes / physiology*


  • Cytokines
  • Interleukin-7