Figure 6.

Proposed mechanisms of enhanced IFNα production in SLE monocytes. Steady-state SLE monocytes exhibit a cellular senescence phenotype as evidenced by CDKN2A upregulation. When exposed to large amounts of self-DNA derived from various triggers such as viruses, apoptotic cells, and NETs, as well as increased mitochondrial DNA (mtDNA) in the cytoplasm, the activation of the cGAS-STING pathway is enhanced in SLE monocytes. This results in the promotion of cellular senescence and GATA4 induction, which further enhances IFNα production. We propose that these mechanisms may be responsible for a vicious cycle of inflammation, especially during an active disease state or flare in SLE patients.