Abstract | BACKGROUND: METHODS: Isolated human CD3+T cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T cells and in polarized TH2 cells using skin-derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay. RESULTS: Treatment of activated human CD4+T cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T cells with RNase 7. CONCLUSION: Our data indicate that RNase 7 has immunomodulatory functions on TH2 cells and decreases the production of TH2 cytokines in the skin.
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Authors | V Kopfnagel, S Wagenknecht, L Brand, J Zeitvogel, J Harder, K Hofmann, M Kleine, T Werfel |
Journal | Allergy
(Allergy)
Vol. 72
Issue 11
Pg. 1694-1703
(Nov 2017)
ISSN: 1398-9995 [Electronic] Denmark |
PMID | 28378334
(Publication Type: Journal Article)
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Copyright | © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. |
Chemical References |
- Cytokines
- GATA3 Transcription Factor
- GATA3 protein, human
- Ribonucleases
- Ribonuclease 7
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Topics |
- Cells, Cultured
- Cytokines
(biosynthesis, drug effects)
- Down-Regulation
(drug effects)
- GATA3 Transcription Factor
(metabolism)
- Humans
- Lymphocyte Activation
- Ribonucleases
(pharmacology)
- Skin
(cytology, metabolism)
- Skin Diseases
(metabolism)
- T-Lymphocytes
(metabolism)
- Th2 Cells
(immunology, metabolism)
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