Cellular sources of pathogenic and protective TNF and experimental strategies based on utilization of TNF humanized mice

Cytokine Growth Factor Rev. 2014 Apr;25(2):115-23. doi: 10.1016/j.cytogfr.2013.12.005. Epub 2013 Dec 24.

Abstract

Over the years, tumor necrosis factor (TNF) has been implicated in the pathogenesis of various inflammatory conditions and TNF antagonists are highly efficient in treatment of multiple autoimmune diseases. However, it has been shown that various cellular sources of TNF exhibit distinct and non-redundant functions that can be either deleterious or beneficial. This suggests that systemic TNF blockade, in addition to neutralization of pathogenic TNF, may abrogate its protective functions, resulting in adverse effects. Here we review the data on cellular sources of pathogenic and protective TNF and then discuss an experimental system based on humanized mice to study the role of cell-type specific TNF ablation during various disease models for development of cell-type specific TNF blockade.

Keywords: Anti-TNF therapy; Colitis; Cytokine; Humanized mice; TNF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Lymphoid Tissue / immunology
  • Mice
  • Receptors, Tumor Necrosis Factor / immunology
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha