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RN ase 7 downregulates TH 2 cytokine production by activated human T cells
Author(s) -
Kopfnagel V.,
Wagenknecht S.,
Brand L.,
Zeitvogel J.,
Harder J.,
Hofmann K.,
Kleine M.,
Werfel T.
Publication year - 2017
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13173
Subject(s) - rnase p , microbiology and biotechnology , ribonuclease , antimicrobial peptides , biology , gata3 , messenger rna , downregulation and upregulation , cytokine , immunology , rna , peptide , biochemistry , gene , transcription factor
Background The antimicrobial peptide ( AMP ) RN ase 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 RN ase 7. In addition to their antimicrobial activity, immunoregulatory functions have been published for several AMP s. In this study, we investigated immunoregulatory effects of the antimicrobial peptide RN ase 7 on activated T cells. Methods Isolated human CD 3+T cells were stimulated with RN ase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD 4+T cells and in polarized TH 2 cells using skin‐derived native RN ase 7 and a recombinant ribonuclease‐inactive RN ase 7 mutant. Activation of GATA 3 was analysed by electrophoretic mobility shift assay. Results Treatment of activated human CD 4+T cells and TH 2 cells with RN ase 7 selectively reduced the expression of TH 2 cytokines ( IL ‐13, IL ‐4 and IL ‐5). Experiments with a ribonuclease‐inactive recombinant RN ase 7 mutant showed that RN ase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD 4+T cells from AD patients revealed a significantly less pronounced downregulation of IL ‐13 in response to RN ase 7 compared to healthy control. Finally, we show that GATA 3 activation was diminished upon cultivation of T cells with RN ase 7. Conclusion Our data indicate that RN ase 7 has immunomodulatory functions on TH 2 cells and decreases the production of TH 2 cytokines in the skin.