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The sorting receptor sortilin exhibits a dual function in exocytic trafficking of interferon-{gamma} and granzyme A in T cells

Official URL:https://doi.org/10.1016/j.immuni.2012.07.012
PubMed:View item in PubMed
Creators Name:Herda, S. and Raczkowski, F. and Mittruecker, H.W. and Willimsky, G. and Gerlach, K. and Kuehl, A.A. and Breiderhoff, T. and Willnow, T.E. and Doerken, B. and Hoepken, U.E. and Rehm, A.
Journal Title:Immunity
Journal Abbreviation:Immunity
Page Range:854-866
Date:16 November 2012
Keywords:Autoimmune Diseases, CD4 Antigens, Cell Membrane, Colitis, Endosomes, Exocytosis, Golgi Apparatus, Granzymes, Inbred C57BL Mice, Interferon-gamma, Interleukin-2 Receptor alpha Subunit, Natural Killer Cells, Protein Transport, R-SNARE Proteins, T-Lymphocytes, Transport Vesicles, Vesicular Transport Adaptor Proteins, Animals, Mice
Abstract: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-{gamma} upon infections and in autoimmune colitis. Exit of interferon-{gamma} from the Golgi apparatus required the presence of Sortilin. Furthermore, we tracked the transport route of interferon-{gamma} beyond this Sortilin-dependent Golgi to early endosome step. In wild-type T cells, trafficking of interferon-{gamma} from the endosomal sorting platform to the plasma membrane proceeded independently of recycling endosomes, and interferon-{gamma} remained excluded from late endosomes. Our results suggest that Sortilin modulates systemic immune responses through exocytic sorting of immunological effector molecules.
Publisher:Cell Press / Elsevier (U.S.A.)
Item Type:Article

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