Association between suppressors of cytokine signalling, T-helper type 1/T-helper type 2 balance and allergic sensitization in children

Clin Exp Allergy. 2008 Mar;38(3):438-48. doi: 10.1111/j.1365-2222.2007.02913.x. Epub 2007 Dec 20.


Background: Suppressors of cytokine signalling (SOCS) family members have been shown to play an important role in the balance of cytokines that determine the onset of T-helper type 1 (Th1)- and Th2-mediated immune responses. In particular, for cytokine-induced Src-homology 2 protein (CIS), SOCS1, SOCS3 and SOCS5, a role in the regulation of T cell differentiation has been discussed. However, only few data exist so far in the human system.

Objectives: The aim of the present study was to analyse the relationship between these suppressors and Th1/Th2 regulation as well as allergic sensitizations within a population-based study.

Methods: Within the Lifestyle-Immune system-Allergy plus cohort study, mRNA was prepared from blood samples of 6-year-old children for the analysis of cytokines, transcription factors for T cell regulation and SOCS molecule expression by quantitative real-time polymerase chain reaction. In addition, total and specific IgE concentrations have been measured by the Pharmacia CAP System. A complete data set from 248 children was available. Results Among the SOCS molecules investigated, only SOCS1 showed a strong positive correlation to allergic sensitizations. In addition, an up-regulated SOCS1 expression correlated with down-regulated T-box expressed in T cells (Tbet) and higher expression levels of GATA-binding protein 3 (GATA-3) and IL-4. No association between SOCS1 and forkhead box P3 (FOXP3) was observed. For SOCS3, SOCS5 and CIS, a contradictory picture was found. The expression of these SOCS molecules was positively correlated with Tbet and FOXP3 and (with the exception of CIS) negatively with IL-4.

Conclusions: Our data suggest that SOCS3, SOCS5 and CIS, which correlate with an up-regulated Th1 and regulatory T cell activity, are without relevance for the allergic status. In contrast, SOCS1 might be involved in the development of a Th2-skewed immune response and subsequent allergic sensitizations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation
  • Child
  • Cohort Studies
  • Female
  • Forkhead Transcription Factors / metabolism
  • GATA3 Transcription Factor / metabolism
  • Humans
  • Hypersensitivity / etiology*
  • Hypersensitivity / metabolism*
  • Hypersensitivity / pathology
  • Interleukin-4 / metabolism
  • Male
  • RNA, Messenger / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Th2 Cells / metabolism*
  • Th2 Cells / pathology
  • Up-Regulation


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • RNA, Messenger
  • SOCS1 protein, human
  • SOCS3 protein, human
  • SOCS5 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • cytokine inducible SH2-containing protein
  • Interleukin-4