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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: |
Herda, S., Raczkowski, F., Mittruecker, H.W., Willimsky, G.  ORCID: https://orcid.org/0000-0002-9693-948X, Gerlach, K., Kuehl, A.A., Breiderhoff, T. ORCID: https://orcid.org/0000-0002-1676-7498, Willnow, T.E. ORCID: https://orcid.org/0000-0001-9515-7921, Doerken, B. ORCID: https://orcid.org/0000-0001-7991-3643, Höpken, U.E. ORCID: https://orcid.org/0000-0002-0776-4893 and Rehm, A. ORCID: https://orcid.org/0000-0001-7490-1950
|
| 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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