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Allergic Asthma

[Translate to en:] Asthma bronchiale

Asthma bronchiale is a worldwide spread disease of the airways, which causes chronic inflammation in the lung. Besides genetic and environmental factors a local activation of the mucosal immune system plays a central role in the origin and perpetuation of the disease. Studies in the past have shown that here especially antigen presenting cells like dendritic cells and T-lymphocytes are involved in the pathogenesis of allergic asthma.

Our group previously showed that proinflammatory cytokines and certain transcription factors in leukocytes are involved in the immuno pathogenesis of asthma bronchiale. Here we investigated in two experimental model systems for asthma: The OVA-model and the HDM-model.

Moreover,we developed a model for tolerogenic asthma. Experiments in the OVA-model showed a central role of the transcription factors GATA-3 and T-bet in allergic asthma. The functional importance of T-bet was highlighted by the findings, that T-bet deficient mice develop a spontaneous Asthma-like phenotype. This phenotype is mediated via IL-13 and can be transfered by T-cells.

Further, we recently discovered a therapeutic effect of intranasal application of the antiviral cytokines IL-28A, IL-28B and IL-29 that are known as IFN lambda. The positive effect of recombinant IL-28A was associated with a reduction of Th2- and Th17-cells in the lung. In addition, IL-28-Receptor deficient mice in our OVA-model of asthma show more severe asthma symptoms than wild type mice. IL-28 receptor deficiency lead to a higher pro-inflammatory cytokine production like IL-6 and less anti-inflammatory cytokines like IFNγ, IL-12 and IL-10 by lung dendritic cells. These dendritic cells regulate the Th2- and Th17 immune response.

In further studies a role of IL-2 and the transcription factor NFATc2 in asthma was analyzed. Specifically we showed that NFATc2 deficiency leads to an enhanced number of CD4+CD25+Foxp3+ regulatory T-cells, which induces immunosuppression in asthma.

Long-term we anticipate, that new therapy strategies can be developed based on these new findings. Particular expectations lie on the modulation of the pro-inflammatory Th2 and Th9 axis and their regulation after activation of protective immune responses.