Endothelial STING controls T cell transmigration in an IFNI-dependent manner

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Stimulator of IFN genes (STING) is a key sensor of cyclic dinucleotides and adaptor for type I IFN (IFNI) signaling.
• T cell infiltration is critical for immune responses, but the mechanisms regulating T cell migration across endothelial barriers are complex.

Purpose of the Study:

• To investigate the role of STING in endothelial cells (EC) during T cell transendothelial migration (TEM).
• To elucidate the molecular mechanisms by which EC-STING influences T cell infiltration.

Main Methods:

• Utilized STING knockout (STING-/-) mice and EC-specific STING knockout mice.
• Assessed T cell infiltration, TEM, and adhesion across mouse and human EC.
• Analyzed the expression of IFNI-stimulated genes (ISGs) like CXCL10.
• Investigated the role of the IFNI receptor (IFNAR) pathway.

Main Results:

• T cell infiltration into the peritoneum was impaired in STING-/- mice.
• T cell TEM across STING-deficient EC was significantly reduced, while adhesion remained unaffected.
• CXCL10, an ISG and T cell chemoattractant, was markedly reduced in TNF-α-stimulated STING-/- EC.
• Blocking the IFNI/IFNAR pathway diminished T cell TEM.

Conclusions:

• Endothelial cell STING plays a critical role in T cell TEM.
• EC-STING-mediated T cell TEM is dependent on the ISG CXCL10 and IFNI/IFNAR signaling.
• These findings highlight a novel function of STING in regulating immune cell trafficking.