Reduced T-bet in addition to enhanced STAT6 and GATA3 expressing T cells contribute to human allergen-induced late responses

Clin Exp Allergy. 2012 Jun;42(6):891-900. doi: 10.1111/j.1365-2222.2012.04003.x.

Abstract

Background: T-bet and GATA-3 are transcriptional factors involved in Th1 and Th2 cell differentiation, although their concomitant roles at protein levels in target organs during human allergic disease have not been assessed.

Objectives: We investigated the expression of T-bet and GATA-3 in nasal and cutaneous models of Th2 (grass-pollen allergen) and a cutaneous model of Th1 (PPD) responses in man.

Methods: Nasal biopsies were obtained at 8 h and skin biopsies at 8 and 48 h after allergen and PPD challenges, respectively, from 10 allergic rhinitics and 6 non-atopic controls. T cells were assessed using immunofluorescence microscopy.

Results: There were increases in CD3(+)STAT6(+)cells (P = 0.01 for nose and skin) and CD3(+)GATA3(+)cells (P = 0.03 for skin) in response to allergen compared with diluent in allergics. When compared with non-atopics after allergen challenge the difference between the two groups was also significant for CD3(+)STAT6(+) (P = 0.001 and 0.03) and for CD3(+)GATA3(+)cells (P = 0.04 and 0.001) for nose and skin respectively. Following PPD challenge CD3(+)STAT4(+)cells and CD3(+)T-bet(+)cells increased in both groups compared with diluent (P = 0.02 and 0.03 for both TFs), whereas only CD3(+)T-bet(+) cells were significantly greater in non-atopics compared with allergics (P = 0.04). The ratio of GATA3(+):T-bet(+) T cells in allergen-induced responses was significantly greater in the allergics (P = 0.008 and 0.01 nose and skin respectively), whereas the ratio of T-bet:GATA3(+)T cells was significantly higher in the non-atopics during PPD-induced responses (P = 0.003).

Conclusions and clinical relevance: Dysregulation of Th1 transcription may contribute to heightened expression of STAT6 and GATA3 leading to exaggerated Th2-driven manifestations of allergic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Female
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • Humans
  • Male
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Rhinitis, Allergic, Seasonal / genetics
  • Rhinitis, Allergic, Seasonal / immunology
  • Rhinitis, Allergic, Seasonal / metabolism
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / metabolism*
  • Skin / immunology
  • Skin / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Young Adult

Substances

  • Allergens
  • GATA3 Transcription Factor
  • STAT6 Transcription Factor
  • T-Box Domain Proteins
  • T-box transcription factor TBX21