| First Author | García-Rodríguez S | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 3357 |
| PubMed ID | 29463868 | Mgi Jnum | J:263067 |
| Mgi Id | MGI:6162952 | Doi | 10.1038/s41598-018-21337-6 |
| Citation | Garcia-Rodriguez S, et al. (2018) CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism. Sci Rep 8(1):3357 |
| abstractText | In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38(-/-)) but not ART2-deficient (Art2(-/-)) 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(hi)Ly6C(hi) inflammatory monocytes, TNF-alpha-producing Ly6G(+) neutrophils and Ly6C(lo) monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis. Cd38(-/-) pristane-elicited peritoneal exudate cells had defective CCL2 and TNF-alpha secretion following TLR7 stimulation. However, Tnf-alpha and Cxcl12 gene expression in Cd38(-/-) bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-alpha/CXCL12 axis in the BM. Chemotactic responses of Cd38(-/-) Ly6C(hi) monocytes and Ly6G(+) neutrophils were not impaired. However, Cd38(-/-) Ly6C(hi) monocytes and Ly6C(lo) monocytes/macrophages had defective apoptosis-mediated cell death. Importantly, mice lacking the cation channel TRPM2 (Trpm2(-/-)) exhibited very similar protection, with decreased numbers of PECs, and apoptotic Ly6C(hi) monocytes and Ly6C(lo) monocytes/macrophages compared to WT mice. These findings reveal a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven mechanism. Furthermore, given the implications of CD38 in the activation of TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is TRPM2-dependent. |
