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Impaired IFN‐α secretion by plasmacytoid dendritic cells induced by TLR9 activation in chronic idiopathic urticaria
Author(s) -
Futata E.,
Azor M.,
Dos Santos J.,
Maruta C.,
Sotto M.,
Guedes F.,
Rivitti E.,
Duarte A.,
Sato M.
Publication year - 2011
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2010.10198.x
Subject(s) - tlr9 , cpg oligodeoxynucleotide , immune system , innate immune system , secretion , immunology , downregulation and upregulation , receptor , dendritic cell , interferon , flow cytometry , cytokine , medicine , biology , microbiology and biotechnology , gene expression , gene , biochemistry , dna methylation
Summary Background Understanding the early events of the immune response, through the activation of plasmacytoid dendritic cells (pDC) by Toll‐like receptor (TLR)9‐sensing, could contribute to the evaluation of immune dysregulation in chronic idiopathic urticaria (CIU). Objectives We decided to investigate innate immunity in CIU and the mechanisms implicated in the modulation of interferon (IFN)‐α production by pDC upon TLR9 activation. Methods Patients with CIU ( n = 31) and healthy control subjects (HC, n = 36) were enrolled in the study. Leucocytes cultured with the TLR9 ligand, CpG type A, or with inhibitory‐oligodeoxynucleotide (ODN) were used to determine IFN‐α secretion by enzyme‐linked immunosorbent assay. Enumeration of pDC, intracellular IFN‐α and signal transducers and activators of transcription protein (STAT) (1 and 4) phosphorylation were assessed by flow cytometry. TLR9 and regulatory factor‐7 mRNA transcripts were evaluated by real‐time polymerase chain reaction. Evidence of pDC in the skin lesions of patients was analysed with immunohistochemistry staining. Results The findings show a decreased IFN‐α secretion induced by CpG A by leucocytes, due to the diminished IFN‐α expression on pDC in CIU. It was mediated by TLR9‐activation since inhibitory‐ODN further suppressed TLR9‐induced IFN‐α secretion. A normal pDC percentage and degree of activation by the expression of costimulatory molecules was observed in CIU, with the rare presence of pDC in the skin lesion. In addition, an increased constitutive STAT1 phosphorylation on nonstimulated lymphocytes and a downregulation of TLR9 mRNA transcripts after CpG A activation were verified in patients with CIU. Conclusions The findings showed an innate immune response in CIU disturbed by impairment of the pDC response to TLR9 activation.