Production of interleukin-13 by human dendritic cells after stimulation with protein allergens is a key factor for induction of T helper 2 cytokines and is associated with activation of signal transducer and activator of transcription-6.
Dendritic cells (DC) are able to induce not only T helper 1 (Th1) but also Th2 immune responses after stimulation with allergens. While DC-derived interleukin (IL)-12 and IL-18 are the key factors for the induction of Th1 cells, early signals being involved in Th2 differentiation are less well characterized so far. To analyse such early signals we used an antigen-specific setting with CD4+ T cells from atopic donors stimulated in the presence of autologous mature DC, which were pulsed with different allergen doses. The addition of increasing amounts of allergen during DC maturation with tumour necrosis factor-alpha, IL-1beta and prostaglandin E2 resulted in enhanced secretion of IL-6 and IL-12 by DC followed by increased production of Th1 (interferon-gamma; IFN-gamma) as well as Th2 (IL-4, IL-5) cytokines by CD4+ T cells. The coculture of allergen-treated DC and CD4+ T cells also led to a dose-dependent expression of active signal transducer and activator of transcription-6 (STAT6), which was visible already after 1 hr. Additionally, rapid phosphorylation of STAT6 was seen in immature DC after stimulation with allergens but not with lipopolysaccharide or human serum albumin. STAT6 phosphorylation was associated with the production of IL-13 by DC. The addition of neutralizing anti-IL-13 antibodies during maturation of DC inhibited STAT6 phosphorylation in CD4+ T cells as well as the production of IL-4, and to a lesser extent of IL-5, while IFN-gamma production was not affected. Addition of exogenous IL-13 enhanced mainly the secretion of IL-4. Taken together, DC-derived IL-13, which is released after exposure to allergens appears to be one of the critical factors for DC to acquire the capability to induce Th2 cytokine production.
Bellinghausen
Iris
I
Department of Dermatology, University of Mainz, Mainz, Germany. bellinghausen@hautklinik.klinik.uni-mainz.de
Brand
Pia
P
Böttcher
Ingo
I
Klostermann
Bettina
B
Knop
Jürgen
J
Saloga
Joachim
J
D000485:Allergens / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism
D000485:Allergens; D016207:Cytokines; D018793:Interleukin-13; D015850:Interleukin-6; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma