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Srikanth, S., Woo, J.S., Wu, B., El-Sherbiny, Y.M. 
ORCID: 0000-0003-4791-3475, Leung, J., Chupradit, K., Rice, L., Seo, G.J., Calmettes, G., Ramakrishna, C., Cantin, E., An, D.S., Sun, R., Wu, T.-T., Jung, J.U., Savic, S. and Gwack, Y.,
2019.
The Ca2+ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum.
Nature Immunology, 20 (2), pp. 152-162.
ISSN 1529-2908
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Abstract
STING is an endoplasmic reticulum (ER) signaling adaptor that is essential for the type I Interferon response to DNA pathogens. Aberrant activation of STING is linked to the pathology of autoimmune and autoinflammatory diseases. The rate-limiting step for the activation of STING is its translocation from the ER to the ER–Golgi intermediate compartment. Here we found that deficiency in the Ca2+ 36 sensor STIM1 caused spontaneous activation of STING and enhanced expression of type I interferons under resting conditions in mice and a patient suffering from combined immunodeficiency. Mechanistically, STIM1 associated with STING to retain it in the ER membrane, and co-expression of full-length or a STING-interacting fragment of STIM1 suppressed the function of dominant STING mutants that cause autoinflammatory diseases. Furthermore, deficiency in STIM1 strongly enhanced the expression of type I interferons after viral infection and prevented the lethality of infection with a DNA virus in vivo. This work delineates a STIM1–STING circuit that maintains the resting state of the STING pathway.
| Item Type: | Journal article | ||||
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| Publication Title: | Nature Immunology | ||||
| Creators: | Srikanth, S., Woo, J.S., Wu, B., El-Sherbiny, Y.M., Leung, J., Chupradit, K., Rice, L., Seo, G.J., Calmettes, G., Ramakrishna, C., Cantin, E., An, D.S., Sun, R., Wu, T.-T., Jung, J.U., Savic, S. and Gwack, Y. | ||||
| Publisher: | Nature Publishing Group | ||||
| Date: | February 2019 | ||||
| Volume: | 20 | ||||
| Number: | 2 | ||||
| ISSN: | 1529-2908 | ||||
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| Divisions: | Schools > School of Science and Technology | ||||
| Record created by: | Jonathan Gallacher | ||||
| Date Added: | 21 Dec 2018 11:30 | ||||
| Last Modified: | 14 Jul 2019 03:00 | ||||
| URI: | https://irep.ntu.ac.uk/id/eprint/35416 |
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