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


OBJECTIVE
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.
Daegelmann
C
C
Department of Environmental Immunology, UFZ - Helmholtz Centre for Environmental Research, Leipzig, Germany.
Herberth
G
G
Röder
S
S
Herbarth
O
O
Giese
T
T
Krämer
U
U
Behrendt
H
H
Borte
M
M
Heinrich
J
J
Emmrich
F
F
Lehmann
I
I
D000917:Antibody Formation; D002648:Child; D015331:Cohort Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; D015847:Interleukin-4; D012333:RNA, Messenger; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C418974:FOXP3 protein, human; C494749:GATA3 protein, human; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; C408990:SOCS5 protein, human