A1 (2016 - 2019) – Regulation and function of in C3aR during the development of allergic asthma

The prevalence of allergic diseases, such as allergic asthma, has continued to rise in developed nations in recent decades. Both animal and human studies have demonstrated that dysregulated production of, or responsiveness to, the anaphylatoxins C3a and C5a influence the development/severity of allergic asthma. In addition to our previous studies investigating the function of C5aR1 in dendritic cells during the allergic asthma development, we recently unravel some aspects of the C5a/C5aR1 functions and its regulation during the sensitization and the effector phase of the disease. Similarly, both association studies in human and animal studies, identified the C3a/C3aR axis as a critical driver of bronchoconstriction during the allergic effector phase. However, the expression, functions, and regulation of C3aR during the course of the disease remain unclear. We will take the opportunity that our lab developed a new C3aR reporter mouse to study both the regulation of C3aR expression during the course of allergic asthma in an house dust mite model (HDM), and to evaluate the impact of a conditional depletion of C3aR in specific cell using cell specific cre mouse strains in the same experimental conditions.  


1: To characterize the expression profile of C3aR in the lung using a Td-Tomato-C3aRflox reporter mouse at steady state or upon HDM-induced allergic asthma conditions.  

2: To define the impact of the conditional deletion of C3aR in an appropriate cre background on the development of an HDM-driven allergic asthma model.