Transcriptomic and proteomic profiling reveals distinct pathogenic features of peripheral non-classical monocytes in systemic lupus erythematosus

Eirini Maria Stergioti; Theodora Manolakou; George Sentis; Martina Samiotaki; Noemin Kapsala; Antonis Fanouriakis; Dimitrios T Boumpas; Aggelos Banos

doi:10.1016/j.clim.2023.109765

Transcriptomic and proteomic profiling reveals distinct pathogenic features of peripheral non-classical monocytes in systemic lupus erythematosus

Clin Immunol. 2023 Oct:255:109765. doi: 10.1016/j.clim.2023.109765. Epub 2023 Sep 9.

Authors

Eirini Maria Stergioti¹, Theodora Manolakou², George Sentis², Martina Samiotaki³, Noemin Kapsala⁴, Antonis Fanouriakis⁴, Dimitrios T Boumpas⁵, Aggelos Banos⁶

Affiliations

¹ Laboratory of Autoimmunity and Inflammation, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, Athens 115 27, Greece; 4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens 124 62, Greece. Electronic address: eirinister@yahoo.gr.
² Laboratory of Autoimmunity and Inflammation, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, Athens 115 27, Greece.
³ Institute for Bioinnovation, Biomedical Sciences Research Center Alexander Fleming, Vari, Athens 166 72, Greece.
⁴ 4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens 124 62, Greece.
⁵ Laboratory of Autoimmunity and Inflammation, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, Athens 115 27, Greece. Electronic address: dboumpas@bioacademy.gr.
⁶ Laboratory of Autoimmunity and Inflammation, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, Athens 115 27, Greece. Electronic address: abanos@bioacademy.gr.

PMID: 37678715
DOI: 10.1016/j.clim.2023.109765

Abstract

Peripheral blood monocytes propagate inflammation in systemic lupus erythematosus (SLE). Three major populations of monocytes have been recognized namely classical (CM), intermediate (IM) and non-classical monocytes (NCM). Herein, we performed a comprehensive transcriptomic, proteomic and functional characterization of the three peripheral monocytic subsets from active SLE patients and healthy individuals. Our data demonstrate extensive molecular disruptions in circulating SLE NCM, characterized by enhanced inflammatory features such as deregulated DNA repair, cell cycle and heightened IFN signaling combined with differentiation and developmental cues. Enhanced DNA damage, elevated expression of p53, G₀ arrest of cell cycle and increased autophagy stress the differentiation potential of NCM in SLE. This immunogenic profile is associated with an activated macrophage phenotype of NCM exhibiting M1 characteristics in the circulation, fueling the inflammatory response. Together, these findings identify circulating SLE NCM as a pathogenic cell type in the disease that could represent an additional therapeutic target.

Keywords: Cell cycle; Cytokines; Differentiation; M1 macrophages; Non-classical monocytes; Systemic lupus erythematosus.