Role of NF-kappaB-dependent proinflammatory mast cell functions in immune responses

• Applicant: Professor Dr. Axel Roers
• Subject Area: Dermatology
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 214654394

Crosslinking of mast cell surface IgE results in rapid release of preformed vasoactive and proinflammatory mediators and, several hours later, additional de novo production of pro-inflammatory mediators. Both these phases are central to the pathogenesis of allergic disease. Numerous other pathways can trigger mast cell activation. In particular, mast cells express pattern recognition receptors suggesting roles in pathogen defense. Functions of mast cells in immune responses were described in kit mutant mouse models of mast cell-deficiency. We have shown, however, that experiments in these mice, can be misleading and have therefore generated novel Cre/loxP-based models for the investigation of mast cell biology. In order to clarify the relevance of pro-inflammatory mast cell functions in immune responses, we created mice with mast cell-specific inactivation or hyperactivation of the pro-inflammatory NF-κB signaling pathway. This was achieved by conditional knock out of the genes encoding IKK2 or NEMO in mast cells, or by mast cell-specific expression of a mutant IKK2 protein, respectively. The present grant aims to characterize these mouse lines for alterations of immune responses, including IgE-mediated responses. Our first results indicate that mast cell NF-κB signaling is essential for T cell and late phase mast cell responses. Contradicting published literature, our data suggest that IKK2 is dispensable for mast cell degranulation.

• DFG Programme: Research Grants
• Participating Person: Professorin Dr. Anne Dudeck