IRF5 and systemic lupus erythematosus: Estrogen promotes proinflammatory signaling by upregulating IRF5, STAT1, NF-κB, RORγt, and HoxC4, while downregulating FoxP3 and AIRE, thereby enhancing cytokine production, T cell survival, and autoantibody generation—mechanisms strongly supported in SLE and pSS models.