Enhanced Th1 Activity and Development of Chronic Enterocolitis in Mice Devoid of Stat3 in Macrophages and Neutrophils

Immunity. 1999 Jan;10(1):39-49. doi: 10.1016/s1074-7613(00)80005-9.

Abstract

We have generated mice with a cell type-specific disruption of the Stat3 gene in macrophages and neutrophils. The mutant mice are highly susceptible to endotoxin shock with increased production of inflammatory cytokines such as TNF alpha, IL-1, IFN gamma, and IL-6. Endotoxin-induced production of inflammatory cytokines is augmented because the suppressive effects of IL-10 on inflammatory cytokine production from macrophages and neutrophils are completely abolished. The mice show a polarized immune response toward the Th1 type and develop chronic enterocolitis with age. Taken together, Stat3 plays a critical role in deactivation of macrophages and neutrophils mainly exerted by IL-10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Chronic Disease
  • Crosses, Genetic
  • DNA-Binding Proteins / genetics*
  • Enterocolitis / genetics*
  • Enterocolitis / immunology*
  • Enterocolitis / pathology
  • Genetic Predisposition to Disease
  • Interleukin-10 / physiology
  • Lipopolysaccharides / toxicity
  • Macrophage Activation / genetics
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Neutrophils / metabolism*
  • STAT3 Transcription Factor
  • Shock, Septic / genetics
  • Shock, Septic / immunology
  • Th1 Cells / immunology*
  • Th1 Cells / pathology
  • Trans-Activators / genetics*

Substances

  • DNA-Binding Proteins
  • Lipopolysaccharides
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Interleukin-10