Garcia-Rodriguez, Sonia and Rosal-Vela, Antonio and Botta, Davide and Cumba Garcia, Luz M. and Zumaquero, Esther and Prados-Maniviesa, Veronica and Cerezo-Wallis, Daniela and Lo Buono, Nicola and Robles-Guirado, Jose-Angel and Guerrero, Salvador and Gonzalez-Paredes, Elena and Andres-Leon, Eduardo and Corbi, Angel and Mack, Matthias and Koch-Nolte, Friedrich and Merino, Ramon and Zubiaur, Mercedes and Lund, Frances E. and Sancho, Jaime (2018) CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism. SCIENTIFIC REPORTS, 8: 3357. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYCLIC ADP-RIBOSE; TIME PCR DATA; T-CELLS; I INTERFERON; GM-CSF; DENDRITIC CELLS; EXPRESSION; ACTIVATION; INDUCTION; TRPM2; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2020 08:46 |
| Last Modified: | 18 Mar 2020 08:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15031 |
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