Impact of STING deficiency on immune response and macrophage polarization 2407

Abstract Description STING, a transmembrane protein located in the endoplasmic reticulum, was initially identified as a key regulator of innate immune responses to viral DNA and has since been implicated in a range of immune functions. In our previous studies, we examined the potential role of STING in MHC-I-mediated antigen presentation. We generated a STING knockout (KO) murine macrophage cell line and treated it with ovalbumin (OVA). This KO line showed reduced internalization, processing, and presentation of the OVA-derived epitope SIINFEKL, independent of OVA protein uptake or proteolysis. Reduced MHC-I surface expression was observed, prompting further exploration of antigen presentation components. Notably, β2-microglobulin levels were decreased, while the peptide-loading machinery (TAPs) remained unaffected. Additionally, JAK-STAT pathway signaling was compromised in response to OVA and LPS treatment in STING KO cells, indicating reduced immune activation. These findings prompted us to investigate STING’s role in macrophage polarization. Using a STING KO line of THP-1 macrophages, we induced M1 and M2 polarization with cytokine cocktails and found, via phosphorylation markers pSTAT1 (M1) and pSTAT6 (M2), a shift towards M2 polarization in STING’s absence. Ongoing studies using human iPSC-derived macrophages aim to further elucidate the molecular mechanisms involved, with additional investigations into STING’s potential role in macrophage differentiation. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)