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Immunity. 2012 Nov 16;37(5):854-66. doi: 10.1016/j.immuni.2012.07.012. Epub 2012 Oct 16.

The sorting receptor Sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells.

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Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.


Immunological control of infections or tumors depends on the release of effector cytokines and polarized secretion of cytotoxic granules from T cells and natural killer cells. Here we show that the sorting receptor Sortilin controlled both processes. In murine Sortilin-deficient cytotoxic T lymphocytes, regulated secretion of granzyme A and cytotoxic killing was enhanced and correlated with increased vesicle-associated membrane protein 7 availability. In contrast, loss of Sortilin reduced the release of interferon-γ upon infections and in autoimmune colitis. Exit of interferon-γ from the Golgi apparatus required the presence of Sortilin. Furthermore, we tracked the transport route of interferon-γ beyond this Sortilin-dependent Golgi to early endosome step. In wild-type T cells, trafficking of interferon-γ from the endosomal sorting platform to the plasma membrane proceeded independently of recycling endosomes, and interferon-γ remained excluded from late endosomes. Our results suggest that Sortilin modulates systemic immune responses through exocytic sorting of immunological effector molecules.

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