title: RNase 7 downregulates TH2 cytokine production by activated human T cells.
abstract: BACKGROUND
  The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity, immunoregulatory functions have been published for several AMPs. In this study, we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T cells.
  
  
  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.
  
  
  CONCLUSIONS
  Our data indicate that RNase 7 has immunomodulatory functions on TH2 cells and decreases the production of TH2 cytokines in the skin.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: V
authors.identifier: http://orcid.org/0000-0002-2060-5643
authors.initials: V
authors.lastname: Kopfnagel
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wagenknecht
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Brand
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Zeitvogel
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Harder
authors.affiliation: PLANTON GmbH, Kiel, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hofmann
authors.affiliation: PLANTON GmbH, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kleine
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Werfel
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D012260:Ribonucleases / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012871:Skin Diseases / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D012260:Ribonucleases; C470000:Ribonuclease 7
keywords: RNase 7; TH2 cytokines; atopic dermatitis