CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism
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CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism. / García-Rodríguez, Sonia; Rosal-Vela, Antonio; Botta, Davide; Cumba Garcia, Luz M; Zumaquero, Esther; Prados-Maniviesa, Verónica; Cerezo-Wallis, Daniela; Lo Buono, Nicola; Robles-Guirado, José-Ángel; Guerrero, Salvador; González-Paredes, Elena; Andrés-León, Eduardo; Corbí, Ángel; Mack, Matthias; Koch-Nolte, Friedrich; Merino, Ramón; Zubiaur, Mercedes; Lund, Frances E; Sancho, Jaime.
In: SCI REP-UK, Vol. 8, No. 1, 20.02.2018, p. 3357.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism
AU - García-Rodríguez, Sonia
AU - Rosal-Vela, Antonio
AU - Botta, Davide
AU - Cumba Garcia, Luz M
AU - Zumaquero, Esther
AU - Prados-Maniviesa, Verónica
AU - Cerezo-Wallis, Daniela
AU - Lo Buono, Nicola
AU - Robles-Guirado, José-Ángel
AU - Guerrero, Salvador
AU - González-Paredes, Elena
AU - Andrés-León, Eduardo
AU - Corbí, Ángel
AU - Mack, Matthias
AU - Koch-Nolte, Friedrich
AU - Merino, Ramón
AU - Zubiaur, Mercedes
AU - Lund, Frances E
AU - Sancho, Jaime
PY - 2018/2/20
Y1 - 2018/2/20
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/s41598-018-21337-6
DO - 10.1038/s41598-018-21337-6
M3 - SCORING: Journal article
C2 - 29463868
VL - 8
SP - 3357
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
ER -