| First Author | Wongchana W | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 11 | Pages | 5337-46 |
| PubMed ID | 26503951 | Mgi Jnum | J:329787 |
| Mgi Id | MGI:6863080 | Doi | 10.4049/jimmunol.1401770 |
| Citation | Wongchana W, et al. (2015) Impact of Notch1 Deletion in Macrophages on Proinflammatory Cytokine Production and the Outcome of Experimental Autoimmune Encephalomyelitis. J Immunol 195(11):5337-46 |
| abstractText | Notch signaling is involved in regulating TLR-mediated responses in activated macrophages. In this study, we investigated the impact of Notch signaling in macrophages in an experimental autoimmune encephalomyelitis (EAE) model. To examine the impact of deficiency in Notch signaling in activated macrophages in EAE, an adoptive transfer of activated macrophages derived from Notch1(fl/fl) x Mx1cre(+/-) (Notch1 knockout [N1KO]) or CSL/Rbp-jkappa(fl/fl) x Mx1cre(+/-) (CSL/RBP-Jkappa KO) mice was performed prior to induction of EAE. Mice receiving activated N1KO macrophages showed decreased severity of EAE compared with mice receiving wild-type or CSL/RBP-Jkappa KO macrophages. In vitro restimulation of splenocytes by myelin oligodendrocyte glycoprotein 35-55 peptide from these mice revealed that cells from mice receiving N1KO macrophages produced significantly less IL-17 compared with the control mice, whereas IFN-gamma production was similar in both groups. We found that activated N1KO, but not CSL/RBP-Jkappa KO, macrophages produced less IL-6 and had lower CD80 expression compared with wild-type and did not exhibit any defect in IL-12p40/70 production, whereas activated macrophages from CSL/RBP-Jkappa KO mice phenocopied gamma-secretase inhibitor treatment for reduced IL-12p40/70 production. Furthermore, the nuclear translocation of the NF-kappaB subunit c-Rel was compromised in gamma-secretase inhibitor-treated and CSL/RBP-Jkappa KO but not N1KO macrophages. These results suggest that Notch1 and CSL/RBP-Jkappa in macrophages may affect the severity of EAE differently, possibly through modulating IL-6 and CD80 expression, which is involved in the Th17 but not Th1 response. |
