Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in atopic dermatitis

Clin Exp Immunol. 2014 Jan;175(1):25-31. doi: 10.1111/cei.12198.

Abstract

T helper type 9 (Th9) cells are a novel identified subset of CD4(+) T helper cells, which could partly contribute to allergic inflammation, while the precise contribution of Th9 cells in atopic dermatitis (AD) remains unknown. We aimed to explore the possible role of Th9 cells in AD pathogenesis. The Th9 cell percentage, transcription factor PU.1 and cytokine interleukin (IL)-9 mRNA levels, as well as IL-9 serum concentration in peripheral circulation, were measured in AD patients, psoriasis patients and healthy controls. The Th9 cell percentage, PU.1 and IL-9 expression levels of AD patients were all increased significantly compared with the other two control groups (P < 0·01), and correlated positively with SCORing Atopic Dermatitis index, serum immunoglobulin (Ig)E and thymus- and activation-regulated chemokine (TARC) levels (P < 0·05). In simple AD patients and AD patients complicated by allergic rhinitis or asthma, there were no significant differences in the Th9 cell percentage, PU.1 and IL-9 expression levels between them. At the same time, IL-9 and vascular endothelial growth factor (VEGF) mRNA levels were detected in AD lesions and normal skin samples, which were both distinctly elevated in AD lesions, and there was a positive association between them (P < 0·01). Keratinocytes were cultured with IL-9 stimulation and the secretion of VEGF was detected. IL-9 can promote the secretion of VEGF by keratinocytes in a time- and dose-dependent manner. In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of AD, which may be supported by the increased release of VEGF by keratinocyes after IL-9 stimulation.

Keywords: IL-9; Th9 cells; atopic dermatitis; vascular endothelial growth factor.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / blood
  • Asthma / complications
  • Asthma / immunology
  • Asthma / pathology
  • Chemokine CCL17 / blood
  • Chemokine CCL17 / immunology
  • Child
  • Child, Preschool
  • Dermatitis, Atopic / blood*
  • Dermatitis, Atopic / complications
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Interleukin-9 / blood*
  • Interleukin-9 / immunology
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Male
  • Proto-Oncogene Proteins / biosynthesis
  • Psoriasis / blood
  • Psoriasis / genetics
  • Psoriasis / immunology
  • Psoriasis / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / immunology
  • Rhinitis, Allergic
  • Rhinitis, Allergic, Perennial / blood
  • Rhinitis, Allergic, Perennial / complications
  • Rhinitis, Allergic, Perennial / immunology
  • Rhinitis, Allergic, Perennial / pathology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • T-Lymphocytes, Helper-Inducer / pathology
  • Trans-Activators / biosynthesis
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / immunology

Substances

  • CCL17 protein, human
  • Chemokine CCL17
  • IL9 protein, human
  • Interleukin-9
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Trans-Activators
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • proto-oncogene protein Spi-1
  • Immunoglobulin E