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

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Item Type:	Article
Title:	The sorting receptor sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells
Creators Name:	Herda, S., Raczkowski, F., Mittruecker, H.W., Willimsky, G., Gerlach, K., Kuehl, A.A., Breiderhoff, T., Willnow, T.E., Doerken, B., Höpken, U.E. and Rehm, A.
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.
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
Source:	Immunity
ISSN:	1074-7613
Publisher:	Cell Press / Elsevier
Volume:	37
Number:	5
Page Range:	854-866
Date:	16 November 2012
Official Publication:	https://doi.org/10.1016/j.immuni.2012.07.012
PubMed:	View item in PubMed

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