Modalities of experimental TNF blockade in vivo: Mouse models

A. A. Kruglov, A. V. Tumanov, S. I. Grivennikov, Yu V. Shebzukhov, A. A. Kuchmiy, G. A. Efimov, M. S. Drutskaya, J. Scheller, D. V. Kuprash, Sergei A. Nedospasov

Research output: Chapter in Book/Report/Conference proceedingConference contribution

8 Scopus citations

Abstract

TNF was originally discovered due to its potent anti-tumor activity in mice but later emerged as one of immune mediators with critical non-redundant functions in health and disease. TNF-deficient mice fail to mount protective responses against intracellular bacteria, such as Listeria or Mycobacteria, partly due to defective bactericidal granuloma formation or its structural maintenance. TNF is also critical for the structure of peripheral lymphoid tissues. On the other hand, pathogenic overproduction of TNF was implicated in several autoimmune diseases, and therapies based on systemic blockade of cytokine signaling are being widely used in clinic. We are using panels of engineered mice with specific inactivation or enhancement of TNF signaling to uncover the fine balance between beneficial and deleterious physiologic functions of TNF. In particular, we have generated mice allowing us to define the source (type of immunocyte) and molecular form (soluble versus membrane-bound) of TNF with non-redundant specific roles in the structural organization of lymphoid tissues, as well as in pathologies, such as EAE or septic shock. Additionally, we have developed novel "humanized" mouse models allowing side-by-side comparison of the effects of clinically used drugs. One of our goals is to design safer modalities of anti-TNF therapy.

Original languageEnglish (US)
Title of host publicationAdvances in TNF Family Research
Subtitle of host publicationProceedings of the 12th International TNF Conference, 2009
EditorsDavid Wallach, Andrew Kovalenko, Marc Feldmann
Pages421-431
Number of pages11
DOIs
StatePublished - Dec 15 2011
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume691
ISSN (Print)0065-2598

Keywords

  • Autoimmunity
  • Mouse models
  • TNF

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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