A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency

Gregory A. Taylor, Ester Carballo, David M. Lee, Wi S. Lai, Michael J. Thompson, Dhavalkumar D. Patel, Daniel I. Schenkman, Gary S. Gilkeson, Hal E. Broxmeyer, Barton F. Haynes, Perry J. Blackshear

Research output: Contribution to journalArticle

577 Scopus citations

Abstract

Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TIP by gene targeting appeared normal at birth, but soon manifested marked medullary and extramedullary myeloid hyperplasia associated with cachexia, erosive arthritis, dermatitis, conjunctivitis, glomerular mesangial thickening, and high titers of anti-DNA and antinuclear antibodies. Myeloid progenitors from these mice showed no increase in sensitivity to growth factors. Treatment of young TTP-deficient mice with antibodies to tumor necrosis factor α (TNFα) prevented the development of essentially all aspects of the phenotype. These results indicate a role for TTP in regulating TNFα synthesis, secretion, turnover, or action. TTP-deficient mice may serve as useful models of the autoimmune inflammatory state resulting from chronic effective TNFα excess.

Original languageEnglish (US)
Pages (from-to)445-454
Number of pages10
JournalImmunity
Volume4
Issue number5
DOIs
StatePublished - May 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency'. Together they form a unique fingerprint.

  • Cite this

    Taylor, G. A., Carballo, E., Lee, D. M., Lai, W. S., Thompson, M. J., Patel, D. D., Schenkman, D. I., Gilkeson, G. S., Broxmeyer, H. E., Haynes, B. F., & Blackshear, P. J. (1996). A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity, 4(5), 445-454. https://doi.org/10.1016/S1074-7613(00)80411-2