Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells

• DOI: 10.1016/j.celrep.2023.113180
• Publication Date: 2023-10-03T14:36:14Z
• Authors: Hannah E. Meibers; Kathrynne A. Warrick; Andrew VonHandorf; Charles N. Vallez; Kiana Kawarizadeh; Irene Saha; Omer Donmez; Viral G. Jain; Leah C. Kottyan; Matthew T. Weirauch; Chandrashekhar Pa...
• Keywords: Sting

Cognate interaction between CD4+ effector memory T (TEM) cells and dendritic (DCs) induces innate inflammatory cytokine production, resulting in detrimental autoimmune pathology storms. While TEM use tumor necrosis factor (TNF) superfamily ligands to activate DCs, whether prompt other DC-intrinsic changes that influence the response has never been investigated. We report surprising discovery trigger double-strand DNA breaks via mitochondrial reactive oxygen species (ROS) production interacting DCs. Initiation of damage DCs activation a cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS)-independent, non-canonical stimulator interferon genes (STING)-TNF receptor-associated 6 (TRAF6)-nuclear κB (NF-κB) signaling axis. Consequently, STING-deficient display reduced NF-κB subsequent defects transcriptional induction functional interleukin-1β (IL-1β) IL-6 following their with cells. The cell-induced inflammation through STING-NF-κB pathway presents this as potential target alleviate cell-driven autoimmunity