Collectively, our study first demonstrated that GRN aggravated ALD-DNA-induced LN via facilitating macrophage M2b polarization, and LN could be ameliorated by down-regulating the expression of GRN in lupus model, thus bringing an insight into better understanding of the underlying mechanism of LN and providing a potential target for clinical therapy. The gene discussed is GRN; the disease is systemic lupus erythematosus.