This study was undertaken to investigate the role of CD38 in a murine model of lupus. Cd38-/- and Cd38-/-/Art2-/- mice, but not Art2-/- mice, developed less severe lupus compared to pristane-treated WT controls, characterized by decreased expression of IFN-I-stimulated genes (ISGs), defective number of peritoneal CCR2hi Ly6Chi inflammatory monocytes, TNF-¿-producing neutrophils, decreased production of anti-single-stranded DNA, anti-nRNP autoantibodies, and ameliorated glomerulonephritis. Using multivariate analyses, increased expression of ISGs plus Tlr7 and Tlr9 genes in pristane-treated peritoneal exudate cells (PECs) discriminated pristane-treated mice from non-treated mice, and within pristane-treated mice those with a milder inflammatory response (Cd38-/- and Cd38-/-/Art2-/-) from those with stronger response (WT and Art2-/-). Similar clustering analyses performed at the onset of the lupus disease indicated that the differences in gene expression between pristane-treated WT and Cd38-/- mice shifted from PECs and BM cells to secondary lymphoid tissues as the spleen. A defective pristane-induced apoptotic-mediated cell death was observed in peritoneal Cd38-/- Ly6Chi monocytes, which may reduce the source of endogenous TLR7 ligands, the driven force for inflammatory cytokine production and B cell differentiation toward autoreactive B cells in lupus. These findings reveal that CD38 may promote aberrant inflammation and lupus-like autoimmunity by an apoptosis-driven caspase-3-dependant mechanism.

This work was supported in part by the European Commission in collaboration with the following Funding Agencies: Junta de Andalucía (J.A.), Consejería Innovación Ciencia y Empresa y Consejería Educación y Ciencia. Proyecto: PC08-CTS-04046 (J.S. y M.Z.). Ministerio de Economía y Cocmpetitividad (MINECO), Proyecto: SAF-2011-27261 (J.S. y M.Z.). A.R.V. was suported by a felllowship-contract from Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía. S.G.R. was supported by a JAEDoc contract from CSIC and a MINECO contract.

Resumen del póster presentado al 4th Madrid Meeting on Dendritic ells and Macrophages, celebrado del 27 al 28 de marzo de 2017 en el Centro Nacional de Biotecnología (CNB-CSIC).-- García-Rodríguez, Sonia et al.

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