SOCS-3 Regulates Onset and Maintenance of T(H)2-mediated Allergic Responses

Nat Med. 2003 Aug;9(8):1047-54. doi: 10.1038/nm896. Epub 2003 Jun 29.

Abstract

Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation between SOCS-3 expression and the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. SOCS-3 transgenic mice showed increased T(H)2 responses and multiple pathological features characteristic of asthma in an airway hypersensitivity model system. In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased T(H)2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of T(H)2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology*
  • Bronchial Hyperreactivity / immunology
  • Bronchial Provocation Tests
  • DNA-Binding Proteins / metabolism
  • Dermatitis, Atopic / immunology*
  • Humans
  • Hypersensitivity / immunology*
  • Hypersensitivity / metabolism
  • Interleukin-12 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proteins / genetics
  • Proteins / metabolism*
  • Repressor Proteins*
  • STAT4 Transcription Factor
  • Signal Transduction / physiology
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Th2 Cells / immunology*
  • Th2 Cells / physiology
  • Trans-Activators / metabolism
  • Transcription Factors*

Substances

  • DNA-Binding Proteins
  • Proteins
  • Repressor Proteins
  • SOCS3 protein, human
  • SOCS5 protein, human
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • Socs3 protein, mouse
  • Socs5 protein, mouse
  • Stat4 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators
  • Transcription Factors
  • Interleukin-12