CD38-deficient (Cd38<sup>-/-</sup>) but not ART2-deficient (Art2<sup>-/-</sup>) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2<sup>hi</sup>Ly6C<sup>hi</sup> inflammatory monocytes, TNF-α-producing Ly6G<sup>+</sup> neutrophils and Ly6C<sup>lo</sup> monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis.