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 Broxmeyer, Barton F. Haynes, Perry J. Blackshear

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

Fingerprint

Tristetraprolin
Cachexia
Autoimmunity
Arthritis
Tumor Necrosis Factor-alpha
Antinuclear Antibodies
Immediate-Early Genes
Conjunctivitis
Gene Targeting
Zinc Fingers
Dermatitis
Hyperplasia
Intercellular Signaling Peptides and Proteins
Transcription Factors
Parturition
Phenotype
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Taylor, G. A., Carballo, E., Lee, D. M., Lai, W. S., Thompson, M. J., Patel, D. D., ... 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

A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. / Taylor, Gregory A.; Carballo, Ester; Lee, David M.; Lai, Wi S.; Thompson, Michael J.; Patel, Dhavalkumar D.; Schenkman, Daniel I.; Gilkeson, Gary S.; Broxmeyer, Hal; Haynes, Barton F.; Blackshear, Perry J.

In: Immunity, Vol. 4, No. 5, 05.1996, p. 445-454.

Research output: Contribution to journalArticle

Taylor, GA, Carballo, E, Lee, DM, Lai, WS, Thompson, MJ, Patel, DD, Schenkman, DI, Gilkeson, GS, Broxmeyer, H, Haynes, BF & Blackshear, PJ 1996, 'A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency', Immunity, vol. 4, no. 5, pp. 445-454. https://doi.org/10.1016/S1074-7613(00)80411-2
Taylor, Gregory A. ; Carballo, Ester ; Lee, David M. ; Lai, Wi S. ; Thompson, Michael J. ; Patel, Dhavalkumar D. ; Schenkman, Daniel I. ; Gilkeson, Gary S. ; Broxmeyer, Hal ; Haynes, Barton F. ; Blackshear, Perry J. / A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. In: Immunity. 1996 ; Vol. 4, No. 5. pp. 445-454.
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