Different regulation of T helper 1- and T helper 2-promoting cytokine signalling factors in human dendritic cells after exposure to protein versus contact allergens.

ABSTRACT

Cytokine-dependent T helper 1 (Th1) differentiation versus T helper 2 (Th2) differentiation is controlled by distinct transcription factors. Previously, we have demonstrated that immature human dendritic cells (DC) from blood donors with allergies show rapid phosphorylation of the Th2-associated signal transducer and activator of transcription 6 (STAT6) upon contact with protein allergens. In the present study we investigated whether this process is regulated by the downstream molecules suppressor of cytokine signalling (SOCS) and/or by the factors T-bet and GATA3. Therefore, immature DC of grass or birch pollen-allergic donors were treated with the respective Th2-promoting protein allergens, and, for comparison, with the Th1-promoting contact allergen 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone (MCI/MI) or with the antigen tetanus toxoid. Changes in the mRNA levels of SOCS1, SOCS3, T-bet and GATA3 were analysed by quantitative real-time polymerase chain reaction. Exposure of DC to protein allergens led to the up-regulation of the Th2-associated genes SOCS3 and GATA3, whereas the contact allergen MCI/MI preferentially enhanced the expression of the Th1-associated gene T-bet. Treatment of immature DC with the antigen tetanus toxoid increased both Th1- and Th2-associated genes. Our data indicate that polarization of type 1 versus type 2 immune responses takes place already at the level of antigen-presenting cells, involving molecules similar to those used in T-cell polarization.