Long-term activation of IFN-I system in SLE induces the expression of CXCL9/10/11, activating CXCR3B-Gs-AC-cAMP-PKA signal pathway to promote the dysfunction of ECs and EPCs; and CXCR3A-Gi-PI3K-MAPK signaling pathway to recruit leukocytes into the inflammatory site. Here, GNAI1 is linked to systemic lupus erythematosus.