Complement Associated Immuno­regulation

My group is interested in settings in which complement, or more specifically the anaphylatoxin C5a and the corresponding receptors C5aR1 and C5aR2, are involved in regulating immune responses or homeostasis. C5a exerts its effector functions through binding and activation of the cognate G-protein-coupled receptors C5aR1 and C5aR2. Both receptors are widely expressed, particularly on immune cells. The role of C5aR1 in inflammation and its downstream effector functions are relatively well described. C5a is considered to mediate most of its proinflammatory actions via this receptor. Accordingly, the ligand/receptor pair C5a/C5R1 has been highlighted as driver of tissue inflammation in several models of autoimmunity. 

The role of the second C5a receptor, C5aR2 is still rather enigmatic and only beginning to emerge. C5aR2 does not bind to G proteins. Consequently, it does not initiate G protein-dependent signaling and was long considered as a mere decoy receptor. Recently, C5aR2 was found to elicit cellular signaling via β-arrestins and to alter the course of tissue inflammation in a pro- or anti-inflammatory manner, depending on the disease model. To illuminate the role of C5aR2, we have recently generated and characterized a floxed tdTomato-C5aR2 reporter mouse in collaboration with the Köhl laboratory. The advantage of the novel C5aR2 reporter mouse is that C5aR2+ cells can be identified without interfering with the function of C5aR2.

The current research of the Karsten laboratory focuses on three topics centered around: 

• The multiple roles of the C5a/C5aR axes in autoimmune bullous dermatoses (AIBD)
• The C5a/C5aR axes as novel regulators of natural killer (NK) cell functions
• The control of B-1 cell dynamics and natural antibody production by the C5a/C5aR axes.