CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism
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-stimulat...
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Nature Portfolio
2018
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oai:doaj.org-article:8fe211be315c44d088247d42cd122a412021-12-02T15:08:06ZCD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism10.1038/s41598-018-21337-62045-2322https://doaj.org/article/8fe211be315c44d088247d42cd122a412018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21337-6https://doaj.org/toc/2045-2322Abstract 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.Sonia García-RodríguezAntonio Rosal-VelaDavide BottaLuz M. Cumba GarciaEsther ZumaqueroVerónica Prados-ManiviesaDaniela Cerezo-WallisNicola Lo BuonoJosé-Ángel Robles-GuiradoSalvador GuerreroElena González-ParedesEduardo Andrés-LeónÁngel CorbíMatthias MackFriedrich Koch-NolteRamón MerinoMercedes ZubiaurFrances E. LundJaime SanchoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-19 (2018) |
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Medicine R Science Q Sonia García-Rodríguez Antonio Rosal-Vela Davide Botta Luz M. Cumba Garcia Esther Zumaquero Verónica Prados-Maniviesa Daniela Cerezo-Wallis Nicola Lo Buono José-Ángel Robles-Guirado Salvador Guerrero Elena González-Paredes Eduardo Andrés-León Ángel Corbí Matthias Mack Friedrich Koch-Nolte Ramón Merino Mercedes Zubiaur Frances E. Lund Jaime Sancho CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism |
| description |
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 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. |
| format |
article |
| author |
Sonia García-Rodríguez Antonio Rosal-Vela Davide Botta Luz M. Cumba Garcia Esther Zumaquero Verónica Prados-Maniviesa Daniela Cerezo-Wallis Nicola Lo Buono José-Ángel Robles-Guirado Salvador Guerrero Elena González-Paredes Eduardo Andrés-León Ángel Corbí Matthias Mack Friedrich Koch-Nolte Ramón Merino Mercedes Zubiaur Frances E. Lund Jaime Sancho |
| author_facet |
Sonia García-Rodríguez Antonio Rosal-Vela Davide Botta Luz M. Cumba Garcia Esther Zumaquero Verónica Prados-Maniviesa Daniela Cerezo-Wallis Nicola Lo Buono José-Ángel Robles-Guirado Salvador Guerrero Elena González-Paredes Eduardo Andrés-León Ángel Corbí Matthias Mack Friedrich Koch-Nolte Ramón Merino Mercedes Zubiaur Frances E. Lund Jaime Sancho |
| author_sort |
Sonia García-Rodríguez |
| title |
CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism |
| title_short |
CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism |
| title_full |
CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism |
| title_fullStr |
CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism |
| title_full_unstemmed |
CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism |
| title_sort |
cd38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and trpm2-dependent mechanism |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/8fe211be315c44d088247d42cd122a41 |
| work_keys_str_mv |
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