Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation

Immunity. 2013 Dec 12;39(6):1158-70. doi: 10.1016/j.immuni.2013.09.016.

Abstract

Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiated into effector cells including macrophages, dendritic cells, and granulocytes and that these cells contributed to type 2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway might operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Flow Cytometry
  • Gene Expression Profiling
  • Hematopoiesis, Extramedullary / immunology*
  • Humans
  • Hypersensitivity / immunology*
  • Inflammation*
  • Mice
  • Mice, Inbred C57BL
  • Polymorphism, Genetic
  • Precursor Cells, B-Lymphoid / cytology
  • Spleen / cytology
  • Spleen / immunology*
  • Trichinellosis / immunology

Substances

  • Cytokines
  • thymic stromal lymphopoietin

Associated data

  • GEO/GSE52485