Larkin et al. provide the first evidence that T cells, much like innate cells, can be activated by STING to produce Type I IFN. Unexpectedly, STING activation in T cells also activated cell stress and death pathways, and affected T cell proliferation (observed in vitro, but not in vivo), calling for evaluation of the effect STING therapies may have on the T cell compartment.
Stimulator of interferon genes (STING) was initially described as a sensor of intracellular bacterial and viral DNA and a promising adjuvant target in innate immune cells; more recently STING has also been shown to detect endogenous DNA and play a role in tumor immunity and autoimmune disease development. Thus far STING has been studied in macrophages and dendritic cells. In this study, to our knowledge we provide the first evidence of STING activation in T cells, in which STING agonists not only provoke type I IFN production and IFN-stimulated gene expression, mirroring the response of innate cells, but are also capable of activating cell stress and death pathways. Our results suggest a re-evaluation of STING agonist-based therapies may be necessary to identify the possible effects on the T cell compartment. Conversely, the effects of STING on T cells could potentially be harnessed for therapeutic applications.
Author Info: (1) Program in Immunology, Sackler Graduate School, Tufts University, Boston, MA (2) Petrozavodsk State University, 185910 Petrozavodsk, Republic of Karelia, Russia. (3) National R
Author Info: (1) Program in Immunology, Sackler Graduate School, Tufts University, Boston, MA (2) Petrozavodsk State University, 185910 Petrozavodsk, Republic of Karelia, Russia. (3) National Research Centre Kurchatov Institute, Centre for Convergence of Nano-, Bio-Information and Cognitive Sciences and Technologies, Moscow 123182, Russia. (4) D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow 117997, Russia. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997, Russia. (5) Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111; and. (6) Program in Immunology, Sackler Graduate School, Tufts University, Boston, MA 02111; Alexander.Poltorak@tufts.edu. Petrozavodsk State University, 185910 Petrozavodsk, Republic of Karelia, Russia. Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA 02111.
