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Immune system promotes the regeneration of liver after surgery through secretion of endogenic messenger substances

(Vienna, 18-02-2016) A research group of the University Clinic Bern and the University Clinic for Surgery of MedUni Vienna discovered that a specific sub-group of cells of the congenital immune system, the so-called "natural killer cells" as well as the "lymphoid-type cells (ILC) of Group 1" can promote the regeneration of the liver after surgery by disbursing endogenic, immune-specific messenger substances (Interleukin 22).


This seems to occur through the increased disbursement of Adenosine Triphosphate (ATP). This is a molecule which, among other, is required as an energy source for the transport of particles within a cell. Also the ATP receptor (P2X1) is modulated. The intercellular communication through the disbursement of regulatory protein (cytokines) is an essential component for the sufficient progression of liver regeneration in human beings. The cytokine "Interleukin 22 (IL-22)", which is produced by immune cells, has already been associated with a certain role in the liver regeneration process.


Researchers in the current study, a cooperation between the University Clinic for Surgery in Bern under Guido Beldi and the University Clinic for Surgery of MedUni under Patrick Starlinger, were able to show that the release of Interleukin 22 occurs from specific cells of the congenital immune system (natural killer cells and lymphoid cells of Group 1) and is associated with postoperative liver regeneration. The work is currently published in the top international journal "Hepatology" (IF 11.06).

References to direct clinical relevance
"As early as in 2013, we were able to demonstrate that a modification of the "natural killer cells" through ATP can have a decisive impact on postoperative liver regeneration. ATP is a molecule which is classified as main energy repository of the cell due to its biochemical characteristics", explains Guido Beldi, "however, if ATP is released from the cells, it has a decisive impact on the signal transmission between cells. A receptor is activated in the course of these ATP-controlled, intercellular transmission of information which, depending on the type, can release different factors and trigger reactions."


Now, it was possible to demonstrate for the first time that ATP can have an essential impact on the regeneration potential of the liver due to the activation of the receptor (P2X1) and the subsequent disbursement of IL-22. This process also seems be of direct clinical relevance. "We are particularly pleased that we have also been able to provide information on the relevance of these mechanisms in human beings. The results indicate that this process plays in fact a pivotal role and could thus also represent a possible therapeutic approach", so Starlinger.

Close cooperation between Vienna and Bern
The Bern-Vienna axis has a long history. Thus, Theodor Billroth (1841- 1917) in Vienna and Theodor Kocher (1841- 1917) in Bern revolutionised thyroid surgery; the principles of this operation are still applied. The close collaboration and extensive correspondence of the two made it possible to analyse and ultimately avoid formerly largely incomprehensible and difficult complications (thyroid hypofunction, parathyroid function disorders).
During the past years, there has once again been an intensive, theoretical knowledge exchange between Bern and Vienna, which also resulted in the research mentioned above. However, consistent rotation has now also developed on a clinical-practical level in order to consolidate, exchange and reinforce the knowledge and expertise of the two centres.

Service: Hepatology
P2X1 regulated IL-22 secretion by innate lymphoid cells is required for efficient liver regeneration. Kudira R, Malinka T, Kohler A, Dosch M, Gomez de Agüero M, Melin N, Haegele S, Starlinger P, Maharjan N, Saxena S, Keogh A, Stroka D, Candinas D, Beldi G.
Hepatology. 2016 Feb 8. doi: 10.1002/hep.28492. [Epub ahead of print]
PMID: 26853442