The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages

Abstract

STING is a transmembrane ER resident protein that was initially described as a regulator of innate immune response triggered by viral DNA and later found to be involved in a broader range of immune processes. Here, we assessed its role in the antigen presentation by generating a STING KO macrophage cell line. In the absence of STING, we observed an impaired OVA-derived SIINFEKL peptide presentation together with a decreased level of MHC-I complex on the plasma membrane, likely due to a decreased mRNA expression of β2 m light chain as no relevant alterations of the peptide-loading complex (TAPs) were found. Moreover, JAK-STAT signaling resulted in impaired STING KO cells following OVA and LPS treatments, suggesting a dampened activation of immune response. Our data revealed a new molecular role of STING in immune mechanisms that could elucidate its role in the pathogenesis of autoimmune disorders and cancer.

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“…Consistent with this, 4T1 M cells secrete higher levels of IL-6, up-regulate cell-surface MHCI, and down-regulate PDL1—all known readouts of STING activity ( Figures S5 B–S5D). 27 , 28 Importantly, these trends are reversed with use of the STING inhibitor, H151 ( Figures S5 B–S5D). Interestingly, 4T1 M tumors show a reduced level of ISGylated proteins ( Figure 5 B), suggesting ISGylation machinery is suppressed or abnormal in these tumors despite robust STING and ISG15 induction.…”