SP 3

Assessment of cytokines, the pivotal messengers in intercellular communication

Cytokines are small messenger proteins that play a decisive role in the communication between the cells of the body. Produced by activated cells, cytokines act on their target cells that bear the specific cytokine receptor. Although cytokines are principally necessary for maintaining body integrity, in some situations they may mediate harmful processes. Regarding the situation after organ transplantation, cytokines are involved in many processes including inflammation of the transplanted organ, but may also support tissue protection and defense against pathogens. Although mostly produced locally in the specific tissue (e.g., in the transplanted organ), cytokines often reach the blood circulation. Here, their levels can be easily quantified and may serve as indicators of the local processes associated with their production.

Cytokines as mediators of inter-cellular communication
Cytokines are mostly produced by activated cells in the tissue (immune cells, tissue cells). Here, they act on cells that bear the specific cytokine receptor. Binding of the cytokine to its cellular receptor induces specific intracellular signals that - depending on the cytokine - support or inhibit different functions/activities of the target cells. These cytokines may also reach the blood circulation, where they can be easily quantified and may serve as indicators of the local processes associated with their production. 

In this subproject, a broad range of cytokines and their modulators (soluble cytokine receptors) will be quantified in blood samples obtained from kidney transplant patients at three different time points after transplantation. Samples from healthy blood donors and patients with chronic inflammatory diseases are available for comparison. The selected cytokines (e.g., IL-17A, IL-19, IL-20, IL-21, IL-29, IL-31) and modulators (e.g., IL-22 binding protein) reflect the activity of different cell populations and include many novel mediators. Since for some of the parameters no reliable detection method is available (e.g., IL-22 binding protein), respective methods will be established (work package 1). Afterwards, blood level will be quantified and - based on their relationships - cytokine networks will be predicted (work package 2). The molecular elements of these networks will then be investigated in cell-/tissue culture-based experiments (work package 3).

Cytokine network

These data together with the other laboratory (expressional, epigenetic, cellular, antibody-related, virus, metabolic) and clinical data of these patients obtained in this consortium will be biometrically integrated to deliver system medicine-based models. This will allow the further understanding of the pathomechanisms, the identification of novel therapeutic targets, and, most importantly, the identification of the individual risk profile in kidney transplant patients (organ rejection versus tolerance, infection/virus reactivation versus viral defense, strength of anti-bacterial competence, tissue destruction versus regeneration, tumor and cardiovascular complications)

Aim of subproject 3