Abstracts (complete list) - Wissenschaft Online

Daniel Hebenstreit, Elisabeth Maier, Jutta Horejs-Hoeck, Min Li-Weber, Albert Duschl
IL-4 suppresses the Gene Expression of TCF-1 in T cells in a
STAT6 dependent way
The Wnt signalling pathway plays an important role in numerous developmental
processes including T cell development. Yet, data on Wnt signalling in mature T cells are
scarce. T cells have a key function in most immune responses and are also associated
with a number of pathologic conditions, such as allergy. T cells involved in the latter are
mainly of the Th2 lineage. Differentiation towards the Th2 type is induced by TCR
engagement following IL-4 stimulation.
The present study focuses on the influence of IL-4 signalling on the Wnt downstream
effector T Cell Factor 1 (TCF-1). Realtime PCR studies on cDNAs from primary human
and mouse T show a decrease of TCF-1 mRNA after stimulation with IL-4. In contrast,
this effect does not occur in STAT6 knock out mice.
By bioinformatics analyses, two STAT6 binding motifs highly conserved between mouse
and human have been identified in the TCF-1 locus. As demonstrated in EMSA, one of
these can bind to STAT6 present in nuclear extracts from IL-4 treated primary human T
cells. To test its repressive effect, this STAT6 binding site was cloned into a plasmid that
carries a highly IL-4 inducible promoter construct of eotaxin 3 and the luciferase
reporter gene. Transfection experiments show that the STAT6 binding site from TCF-1
reduces luciferase activity significantly, whereas a mutated version does not.
Briefly, our current findings have identified STAT6 to be responsible for the IL-4 induced
suppression of TCF-1.