To transport substances from the site of their production to their destination, the body needs a sophisticated transport and sorting system. Various receptors in and on the cells recognize certain molecules, pack them and ensure that they are transported to the right place. One of these receptors is Sortilin. It is present in the cells of the nervous system, the liver, and the immune system. Studies by Stefanie Herda and Dr. Armin Rehm (Max Delbr-ck Center for Molecular Medicine, MDC, Berlin-Buch and Charit-Universit-tsmedizin Berlin) and the immunologist Dr. Uta H-pken (MDC) have now shown that the receptor Sortilin plays an important role in the function of the immune system (Immunity, doi: 10.1016/j.immuni.2012.07.012)*.
In the search for diseases, the T cells of the immune system go on patrol throughout the body. If they encounter a cell infected by viruses, they bind to it and secrete substances that ensure that the target cell dies. One of these substances is granzyme A, which penetrates the infected cell and induces programmed cell death. In addition, the immune cells secrete interferon-gamma, which induces the surrounding cells to have a stronger immune response.
Interferon-gamma is produced by cytotoxic T cells (formerly: T killer cells), T helper cells and natural killer cells. It enhances the activity of immune cells and induces other cells of the body to increasingly present fragments of the pathogen on their surface so that the T cells can find the affected cells more easily. To facilitate the transport of interferon-gamma from the interior of the T cell where it is produced to the cell membrane where it can be released, the cell uses its interior processing and transport system, to which the Golgi apparatus belongs.
If one were to imagine the Golgi apparatus as a post office, Sortilin's task is to wrap the interferon-gamma cargo into these packages and navigate them to their destination. Without Sortilin, however, the packages cannot be delivered and remain in the post office, that is in the Golgi apparatus. Correspondingly, in the serum, i.e. outside of the cell, too little interferon-gamma is present. Thus, lack of interferon-gamma is not caused by diminished production, but rather by reduced or abrogated transport activity, eventually preventing the interferon-gamma from reaching its destination. This in turn leads to a weakened immune defense system since the interferon can only exert its immune-stimulating effect when it is released from the immune cells.