Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response

• DOI: 10.1016/j.xcrm.2023.101333
• Publication Date: 2023-12-19T15:45:37Z
• Authors: Camille de Cevins; Laure Delage; Maxime Batignes; Quentin Riller; Marine Luka; Anne Remaury; Boris Sorin; Tinhinane Fali; Cécile Masson; Bénédicte Hoareau; Catherine Meunier; Mélanie Parisot; Mohammed Zarhrate; Brieuc P. Pérot; Víctor García-Par...; Francesco Carbone; Lou Galliot; Béatrice Nal; Philippe Pierre; Luc Canard; Charlotte Boussard; Etienne Crickx; Jean-Claude Guill...; Brigitte Bader-Me...; Alexandre Bélot; Pierre Quartier; Marie-Louise Frémond; Bénédicte Neven; Galina Boldina; Franck Augé; Fischer Alain; Michel Didier; Frédéric Rieux-La...; Mickaël M. Ménager
• Keywords: Monocyte

Gain-of-function mutations in stimulator of interferon gene 1 (STING1) result STING-associated vasculopathy with onset infancy (SAVI), a severe autoinflammatory disease. Although elevated type I (IFN) production is thought to be the leading cause symptoms observed patients, STING can induce set pathways, which have roles and severity SAVI remain elucidated. To this end, we performed multi-omics comparative analysis peripheral blood mononuclear cells (PBMCs) plasma from patients healthy controls, combined dataset PBMCs treated IFN-β. Our data reveal subset disease-associated monocyte, expressing CCL3, CCL4, IL-6, as well strong integrated stress response, suggest direct PERK activation by STING. Cell-to-cell communication inference indicates that these monocytes lead T cell early activation, resulting their senescence apoptosis. Last, propose transcriptomic signature independent IFN response.