Send to

Choose Destination
Sci Rep. 2018 Feb 20;8(1):3357. doi: 10.1038/s41598-018-21337-6.

CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism.

Author information

Department of Cellular Biology and Immunology, IPBLN-CSIC, Granada, Spain.
Department of Microbiology, UAB, Birmingham, Alabama, USA.
Immunology Graduate Program, Mayo Clinic, Rochester, MN, USA.
Melanoma Group, CNIO, Madrid, Spain.
Laboratory of Immune-mediated Diseases, San Raffaele Diabetes Research Institute (DRI), Milano, Italy.
Flow Cytometry Unit, IPBLN-CSIC, Granada, Spain.
Bioinformatics Unit, IPBLN-CSIC, Granada, Spain.
Department of Molecular Microbiology and Infection Biology, CIB-CSIC, Madrid, Spain.
Department of Internal Medicine II, Nephrology, Regensburg University Medical Center, Regensburg, Germany.
Institute of Immunology, University Medical Center Eppendorf-Hamburg, Hamburg, Germany.
Department of Molecular and Cellular Signalling, IBBTEC-CSIC-UC, Santander, Spain.
Department of Cellular Biology and Immunology, IPBLN-CSIC, Granada, Spain.


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 CCR2hiLy6Chi inflammatory monocytes, TNF-α-producing Ly6G+ neutrophils and Ly6Clo 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-α secretion following TLR7 stimulation. However, Tnf-α and Cxcl12 gene expression in Cd38-/- bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-α/CXCL12 axis in the BM. Chemotactic responses of Cd38-/- Ly6Chi monocytes and Ly6G+ neutrophils were not impaired. However, Cd38-/- Ly6Chi monocytes and Ly6Clo 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 Ly6Chi monocytes and Ly6Clo 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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center