Arbeitsgruppe Prof. Mahnke
Immunology of Dendritic cells and Regulatory T cells and their interplay
Dendritic cells (DC) are the pivotal inducers of immunity, whereas regulatory T cells (Treg) push the brakes on immune reactions. This interplay between pro-inflammatory and anti-inflammatory mechanisms is investigated in different models.
DC are stimulatory once activated. However, in the absence of “danger” and activation DC can induce tolerance. For therapeutic use we devised a system to load DC in vivo with DC specific antibodies, carrying antigens of interest to the DC. These antibody-antigen conjugates are taken up and presented to T-cells in a non-stimulatory way. Treg are activated leading to tolerance and immune suppression. This tolerogenic approach was successful in allergic contact dermatitis and in EAE. We are now on our way to elucidate the molecular mechanisms underlying the induction of “tolerogenic DC” by antigen targeting.
Treg derived adenosine as suppressive mediator
We have established that Treg interact with DC inducing a tolerogenic phenotype of DC. The means of this interaction are not fully understood. However, we have demonstrated a crucial role of adenosine in guiding this interaction. Adenosine is produced by Treg by degradation of ATP into adenosine and adenosine acts as suppressive second messenger, suppressing a wide array of immune functions.
- Haptene induzieren Freisetzung von ATP in der Haut.
- Treg, Langerhans-Zellen und Keratinozyten exprimieren CD39 und CD73 und degradieren ATP zu Adenosin.
- Adenosin wirkt auf Endothelzellen und verhindert die Expression von P- und E-Selektin.
- Dadurch wird die Rekrutierung von Effektor T-Zellen in das Gewebe vermindert.
- Suppression des Kontaktekzems.
Current Animal Models
- Murine Model of contact hypersensitivity reaction (CHS)
- Murine Model of experimental allergic encephalomyelitis (EAE)
- In vivo microscopy (skinfold chamber)
- Investigation of lymphocyte - endothelial cell interaction
- In vitro generated Dendritic cells
- Cellular immune therapy (Treg, DC)